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Journal Cover Wiley Interdisciplinary Reviews : RNA
   Journal TOC RSS feeds Export to Zotero [3 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Online) 1757-7012
     Published by John Wiley and Sons Homepage  [1603 journals]   [SJR: 2.692]   [H-I: 10]
  • Cotranscriptional events in eukaryotic ribosome synthesis
    • Authors: Tomasz W. Turowski; David Tollervey
      Abstract: Eukaryotic ribosomes are synthesized in a complex, multistep pathway. This begins with transcription of the rDNA genes by a specialized RNA polymerase, accompanied by the cotranscriptional binding of large numbers of ribosome synthesis factors, small nucleolar RNAs and ribosomal proteins. Cleavage of the nascent transcript releases the early pre‐40S and pre‐60S particles, which acquire export competence in the nucleoplasm prior to translocation through the nuclear pore complexes and final maturation to functional ribosomal subunits in the cytoplasm. This review will focus on the many and complex interactions occurring during pre‐rRNA synthesis, particularly in budding yeast in which the pathway is best understood. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-08-29T14:43:19.204744-05:
      DOI: 10.1002/wrna.1263
       
  • The RNAissance family: SR proteins as multifaceted regulators of gene
           expression
    • Authors: Jonathan M. Howard; Jeremy R. Sanford
      Abstract: Serine and arginine‐rich (SR) proteins play multiple roles in the eukaryotic gene expression pathway. Initially described as constitutive and alternative splicing factors, now it is clear that SR proteins are key determinants of exon identity and function as molecular adaptors, linking the pre‐messenger RNA (pre‐mRNA) to the splicing machinery. In addition, now SR proteins are implicated in many aspects of mRNA and noncoding RNA (ncRNA) processing well beyond splicing. These unexpected roles, including RNA transcription, export, translation, and decay, may prove to be the rule rather than the exception. To simply define, this family of RNA‐binding proteins as splicing factors belies the broader roles of SR proteins in post‐transcriptional gene expression. Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.
      PubDate: 2014-08-22T18:18:44.677454-05:
      DOI: 10.1002/wrna.1260
       
  • RNA triplexes: from structural principles to biological and biotech
           applications
    • Authors: Gitali Devi; Yuan Zhou, Zhensheng Zhong, Desiree‐Faye Kaixin Toh, Gang Chen
      Abstract: The diverse biological functions of RNA are determined by the complex structures of RNA stabilized by both secondary and tertiary interactions. An RNA triplex is an important tertiary structure motif that is found in many pseudoknots and other structured RNAs. A triplex structure usually forms through tertiary interactions in the major or minor groove of a Watson–Crick base‐paired stem. A major‐groove RNA triplex structure is stable in isolation by forming consecutive major‐groove base triples such as U·A‐U and C+·G‐C. Minor‐groove RNA triplexes, e.g., A‐minor motif triplexes, are found in almost all large structured RNAs. As double‐stranded RNA stem regions are often involved in biologically important tertiary triplex structure formation and protein binding, the ability to sequence specifically target any desired RNA duplexes by triplex formation would have great potential for biomedical applications. Programmable chemically modified triplex‐forming oligonucleotides (TFOs) and triplex‐forming peptide nucleic acids (PNAs) have been developed to form TFO·RNA2 and PNA·RNA2 triplexes, respectively, with enhanced binding affinity and sequence specificity at physiological conditions. Here, we (1) provide an overview of naturally occurring RNA triplexes, (2) summarize the experimental methods for studying triplexes, and (3) review the development of TFOs and triplex‐forming PNAs for targeting an HIV‐1 ribosomal frameshift‐inducing RNA, a bacterial ribosomal A‐site RNA, and a human microRNA hairpin precursor, and for inhibiting the RNA–protein interactions involving human RNA‐dependent protein kinase and HIV‐1 viral protein Rev. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-08-22T04:57:21.390679-05:
      DOI: 10.1002/wrna.1261
       
  • CLP1 as a novel player in linking tRNA splicing to neurodegenerative
           disorders
    • Authors: Stefan Weitzer; Toshikatsu Hanada, Josef M. Penninger, Javier Martinez
      Abstract: Defects in RNA metabolic pathways are well‐established causes for neurodegenerative disorders. Several mutations in genes involved in pre‐messenger RNA (pre‐mRNA) and tRNA metabolism, RNA stability and protein translation have been linked to motor neuron diseases. Our study on a mouse carrying a catalytically inactive version of the RNA kinase CLP1, a component of the tRNA splicing endonuclease complex, revealed a neurological disorder characterized by progressive loss of lower spinal motor neurons. Surprisingly, mutant mice accumulate a novel class of tRNA‐derived fragments. In addition, patients with homozygous missense mutations in CLP1 (R140H) were recently identified who suffer from severe motor‐sensory defects, cortical dysgenesis and microcephaly, and exhibit alterations in transfer RNA (tRNA) splicing. Here, we review functions of CLP1 in different RNA pathways and provide hypotheses on the role of the tRNA splicing machinery in the generation of tRNA fragments and the molecular links to neurodegenerative disorders. We further immerse the biology of tRNA splicing into topics of (t)RNA metabolism and oxidative stress, putting forward the idea that defects in tRNA processing leading to tRNA fragment accumulation might trigger the development of neurodegenerative diseases. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-08-20T09:42:52.013605-05:
      DOI: 10.1002/wrna.1255
       
  • Issue information
    • PubDate: 2014-08-18T06:08:04.142961-05:
      DOI: 10.1002/wrna.1259
       
  • microRNAs: role in leukemia and their computational perspective
    • Authors: Ankur Omer; Poonam Singh, Navneet Kumar Yadav, Rama Kant Singh
      Pages: n/a - n/a
      Abstract: MicroRNAs (miRNAs) belong to the family of noncoding RNAs (ncRNAs) and had gained importance due to its role in complex biochemical pathways. Changes in the expression of protein coding genes are the major cause of leukemia. Role of miRNAs as tumor suppressors has provided a new insight in the field of leukemia research. Particularly, the miRNAs mediated gene regulation involves the modulation of multiple mRNAs and cooperative action of different miRNAs to regulate a particular gene expression. This highly complex array of regulatory pathway network indicates the great possibility in analyzing and identifying novel findings. Owing to the conventional, slow experimental identification process of miRNAs and their targets, the last decade has witnessed the development of a large amount of computational approaches to deal with the complex interrelations present within biological systems. This article describes the various roles played by miRNAs in regulating leukemia and the role of computational approaches in exploring new possibilities. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-08-15T16:30:40.780936-05:
      DOI: 10.1002/wrna.1256
       
  • RNA structural analysis by evolving SHAPE chemistry
    • Authors: Robert C. Spitale; Ryan A. Flynn, Eduardo A. Torre, Eric T. Kool, Howard Y. Chang
      Pages: n/a - n/a
      Abstract: RNA is central to the flow of biological information. From transcription to splicing, RNA localization, translation, and decay, RNA is intimately involved in regulating every step of the gene expression program, and is thus essential for health and understanding disease. RNA has the unique ability to base‐pair with itself and other nucleic acids to form complex structures. Hence the information content in RNA is not simply its linear sequence of bases, but is also encoded in complex folding of RNA molecules. A general chemical functionality that all RNAs have is a 2′‐hydroxyl group in the ribose ring, and the reactivity of the 2′‐hydroxyl in RNA is gated by local nucleotide flexibility. In other words, the 2′‐hydroxyl is reactive at single‐stranded and conformationally flexible positions but is unreactive at nucleotides constrained by base‐pairing. Recent efforts have been focused on developing reagents that modify RNA as a function of RNA 2′ hydroxyl group reactivity. Such RNA structure probing techniques can be read out by primer extension in experiments termed RNA SHAPE (selective 2′‐ hydroxyl acylation and primer extension). Herein, we describe the efforts devoted to the design and utilization of SHAPE probes for characterizing RNA structure. We also describe current technological advances that are being applied to utilize SHAPE chemistry with deep sequencing to probe many RNAs in parallel. The merging of chemistry with genomics is sure to open the door to genome‐wide exploration of RNA structure and function. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-08-15T15:53:40.751254-05:
      DOI: 10.1002/wrna.1253
       
  • Noncoding RNAs and the borders of heterochromatin
    • Authors: Allison L. Cohen; Songtao Jia
      Abstract: Eukaryotic genomes contain long stretches of repetitive DNA sequences, which are the preferred sites for the assembly of heterochromatin structures. The formation of heterochromatin results in highly condensed chromosomal domains that limit the accessibility of DNA to the transcription and recombination machinery to maintain genome stability. Heterochromatin has the tendency to spread, and the formation of boundaries that block heterochromatin spreading is required to maintain stable gene expression patterns. Recent work has suggested that noncoding RNAs (ncRNAs) are involved in regulating boundary formation in addition to their well‐established roles in chromatin regulation. Here, we present a review of our current understanding of the involvement of ncRNA at the boundaries of heterochromatin, highlighting their mechanisms of action in different settings. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-09T14:10:37.517848-05:
      DOI: 10.1002/wrna.1249
       
  • Not miR‐ly micromanagers: the functions and regulatory networks of
           microRNAs in mammalian skin
    • Authors: Kent Riemondy; Jaimee E Hoefert, Rui Yi
      Abstract: The microRNA (miRNA) pathway is a widespread mechanism of post‐transcriptional gene regulation in eukaryotic cells. In animals, each miRNA species can regulate hundreds of protein‐coding genes, resulting in pervasive functions for miRNAs in numerous cellular processes. Since the identification of the first mammalian miRNA, the function of miRNAs in mammals has been a topic of great interest, both because of the versatile roles of miRNAs in biological systems, as well as the clinical potential of these regulatory RNAs. With well‐defined cell lineages and the availability of versatile tools for both in vivo and in vitro studies, mammalian skin has emerged as an important system in which to examine miRNAs' functions in adult tissues. In this review, we discuss recent insights into the functions and regulatory networks of miRNAs in mammals, with a specific focus on murine skin development as a model system. We first introduce functional analyses of the miRNA biogenesis pathway in the skin, then highlight the functions of individual miRNAs in skin development, followed by an examination of miRNA roles in skin stress responses. We finish with a discussion of miRNA regulatory networks and emphasize future challenges and emerging technologies that permit the genome‐wide study of miRNA functions and regulatory mechanisms in mammalian skin. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-09T14:10:35.411882-05:
      DOI: 10.1002/wrna.1250
       
  • Structure and function of pseudoknots involved in gene expression control
    • Authors: Alla Peselis; Alexander Serganov
      Abstract: Natural RNA molecules can have a high degree of structural complexity but even the most complexly folded RNAs are assembled from simple structural building blocks. Among the simplest RNA elements are double‐stranded helices that participate in the formation of different folding topologies and constitute the major fraction of RNA structures. One common folding motif of RNA is a pseudoknot, defined as a bipartite helical structure formed by base‐pairing of the apical loop in the stem‐loop structure with an outside sequence. Pseudoknots constitute integral parts of the RNA structures essential for various cellular activities. Among many functions of pseudoknotted RNAs is feedback regulation of gene expression, carried out through specific recognition of various molecules. Pseudoknotted RNAs autoregulate ribosomal and phage protein genes in response to downstream encoded proteins, while many metabolic and transport genes are controlled by cellular metabolites interacting with pseudoknotted RNA elements from the riboswitch family. Modulation of some genes also depends on metabolite‐induced messenger RNA (mRNA) cleavage performed by pseudoknotted ribozymes. Several regulatory pseudoknots have been characterized biochemically and structurally in great detail. These studies have demonstrated a plethora of pseudoknot‐based folds and have begun uncovering diverse molecular principles of the ligand‐dependent gene expression control. The pseudoknot‐mediated mechanisms of gene control and many unexpected and interesting features of the regulatory pseudoknots have significantly advanced our understanding of the genetic circuits and laid the foundation for modulation of their outcomes. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-08T07:34:37.61093-05:0
      DOI: 10.1002/wrna.1247
       
  • The role of microRNA in resistance to breast cancer therapy
    • Authors: Neil M. Robertson; Mehmet V. Yigit
      Abstract: MicroRNAs (miRNAs) are small noncoding RNA molecules with big implications in cancer. The abnormal expression of specific miRNAs has been linked to development of many cancer types. Dysregulated miRNAs play a significant role in proliferation, invasion, differentiation, apoptosis, and resistance of various cancer cells, and considered as oncogenes or tumor‐suppressor genes. Findings have shown abnormal expression of specific miRNAs in breast tumors is a strong indication about the resistance to conventional cancer therapy methods. Acquired cancer resistance is a complex, multifactorial occurrence that requires various mechanisms and processes, however, recent studies have suggested that resistance may be linked to treatment‐induced dysregulation of miRNAs. This dysregulation of miRNAs can affect the protein expression in cells, the ability for anti‐cancer drugs to reach their targets within cells, and the apoptotic pathways. Controlling the expression of these miRNAs alters the resistant phenotype of breast cancer to a nonresistant one. This review focuses on the role of dysregulated miRNAs in breast cancer that are linked to resistance against chemo‐, radiation, hormone, and targeted therapies. Finally, the role of miRNAs in breast cancer metastasis is briefly discussed. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-08T07:34:31.546054-05:
      DOI: 10.1002/wrna.1248
       
  • Novel viral translation strategies
    • Authors: Hilda HT Au; Eric Jan
      Abstract: Viral genomes are compact and encode a limited number of proteins. Because they do not encode components of the translational machinery, viruses exhibit an absolute dependence on the host ribosome and factors for viral messenger RNA (mRNA) translation. In order to recruit the host ribosome, viruses have evolved unique strategies to either outcompete cellular transcripts that are efficiently translated by the canonical translation pathway or to reroute translation factors and ribosomes to the viral genome. Furthermore, viruses must evade host antiviral responses and escape immune surveillance. This review focuses on some recent major findings that have revealed unconventional strategies that viruses utilize, which include usurping the host translational machinery, modulating canonical translation initiation factors to specifically enhance or repress overall translation for the purpose of viral production, and increasing viral coding capacity. The discovery of these diverse viral strategies has provided insights into additional translational control mechanisms and into the viral host interactions that ensure viral protein synthesis and replication. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-08T07:21:11.265553-05:
      DOI: 10.1002/wrna.1246
       
  • Novel roles of the CCR4–NOT complex
    • Authors: Clément Chapat; Laura Corbo
      Abstract: The CCR4–NOT complex is a multi‐subunit protein complex evolutionarily conserved across eukaryotes which regulates several aspects of gene expression. A fascinating model is emerging in which this complex acts as a regulation platform, controlling gene products ‘from birth to death’ through the coordination of different cellular machineries involved in diverse cellular functions. Recently the CCR4–NOT functions have been extended to the control of the innate immune response through the regulation of interferon signaling. Thus, a more comprehensive picture of how CCR4–NOT allows the rapid adaptation of cells to external stress, from transcription to mRNA and protein decay, is presented and discussed here. Overall, CCR4–NOT permits the efficient and rapid adaptation of cellular gene expression in response to changes in environmental conditions and stimuli. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-08T07:14:19.330063-05:
      DOI: 10.1002/wrna.1254
       
  • Small noncoding RNAs and male infertility
    • Authors: Lan‐Tao Gou; Peng Dai, Mo‐Fang Liu
      Abstract: Small noncoding RNAs (ncRNAs) are a novel class of gene regulators that modulate gene expression at transcriptional, post‐transcriptional, and epigenetic levels, and they play crucial roles in almost all cellular processes in eukaryotes. Recent studies have indicated that several types of small noncoding RNAs, including microRNAs (miRNAs), endo‐small interference RNAs (endo‐siRNAs), and Piwi‐interacting RNAs (piRNAs), are expressed in the male germline and are required for spermatogenesis in animals. In this review, we summarize the recent knowledge of these small noncoding RNAs in male germ cells and their biological functions and mechanisms of action in animal spermatogenesis. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-08T06:43:41.153365-05:
      DOI: 10.1002/wrna.1252
       
  • The regulatory potential of upstream open reading frames in eukaryotic
           gene expression
    • Authors: Klaus Wethmar
      Abstract: Upstream open reading frames (uORFs) are prevalent cis‐regulatory sequence elements in the transcript leader sequences (TLSs) of eukaryotic mRNAs. The majority of uORFs is considered to repress downstream translation by the consumption of functional pre‐initiation complexes or by inhibiting unrestrained progression of the ribosome. Under distinct conditions, specific uORF properties or sequential arrangements of uORFs can oppositely confer enhanced translation of the main coding sequence, designating uORFs as versatile modifiers of gene expression. Ribosome profiling and proteomic studies demonstrated widespread translational activity at AUG‐ and non‐AUG‐initiated uORFs in eukaryotic transcriptomes from yeast to human and several reports linked defective uORF‐mediated translational control to the development of human diseases. This review summarizes the structural features affecting uORF‐mediated translational control in eukaryotes and describes the highly divergent mechanisms of uORF regulation that result in repression or induction of downstream protein translation. For further resources related to this article, please visit the WIREs website. Conflict of interest: The author has declared no conflicts of interest for this article.
      PubDate: 2014-07-03T10:27:11.451576-05:
      DOI: 10.1002/wrna.1245
       
  • The 100S ribosome: ribosomal hibernation induced by stress
    • Authors: Hideji Yoshida; Akira Wada
      Pages: n/a - n/a
      Abstract: One of the most important cellular events in all organisms is protein synthesis (translation), which is catalyzed by ribosomes. The regulation of translational activity is dependent on the environmental situation of the cell. A decrease in overall translation under stress conditions is mainly accompanied by the formation of functionally inactive 100S ribosomes in bacteria. The 100S ribosome is a dimer of two 70S ribosomes that is formed through interactions between their 30S subunits. Two mechanisms of 100S ribosome formation are known: one involving ribosome modulation factor (RMF) and short hibernation promoting factor (HPF) in a part of Gammaproteobacteria including Escherichia coli, and the other involving only long HPF in the majority of bacteria. The expression of RMF is regulated by ppGpp and cyclic AMP-cAMP receptor protein (cAMP-CRP) induced by amino acid starvation and glucose depletion, respectively. When stress conditions are removed, the 100S ribosome immediately dissociates into the active 70S ribosomes by releasing RMF. The stage in the ribosome cycle at which the ribosome loses translational activity is referred to as ‘Hibernation’. The lifetime of cells that cannot form 100S ribosomes by deletion of the rmf gene is shorter than that of parental cells under stress conditions in E. coli. This fact indicates that the interconversion system between active 70S ribosomes and inactive 100S ribosomes is an important survival strategy for bacteria. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-06-18T08:07:33.466334-05:
      DOI: 10.1002/wrna.1242
       
  • Interrelations between translation and general mRNA degradation in yeast
    • Authors: Susanne Huch; Tracy Nissan
      Pages: n/a - n/a
      Abstract: Messenger RNA (mRNA) degradation is an important element of gene expression that can be modulated by alterations in translation, such as reductions in initiation or elongation rates. Reducing translation initiation strongly affects mRNA degradation by driving mRNA toward the assembly of a decapping complex, leading to decapping. While mRNA stability decreases as a consequence of translational inhibition, in apparent contradiction several external stresses both inhibit translation initiation and stabilize mRNA. A key difference in these processes is that stresses induce multiple responses, one of which stabilizes mRNAs at the initial and rate-limiting step of general mRNA decay. Because this increase in mRNA stability is directly induced by stress, it is independent of the translational effects of stress, which provide the cell with an opportunity to assess its response to changing environmental conditions. After assessment, the cell can store mRNAs, reinitiate their translation or, alternatively, embark on a program of enhanced mRNA decay en masse. Finally, recent results suggest that mRNA decay is not limited to non-translating messages and can occur when ribosomes are not initiating but are still elongating on mRNA. This review will discuss the models for the mechanisms of these processes and recent developments in understanding the relationship between translation and general mRNA degradation, with a focus on yeast as a model system. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-06-18T07:55:27.467807-05:
      DOI: 10.1002/wrna.1244
       
  • Influence of miRNA in insulin signaling pathway and insulin resistance:
           micro-molecules with a major role in type-2 diabetes
    • Authors: Chiranjib Chakraborty; C. George Priya Doss, Sanghamitra Bandyopadhyay, Govindasamy Agoramoorthy
      Pages: n/a - n/a
      Abstract: The prevalence of type-2 diabetes (T2D) is increasing significantly throughout the globe since the last decade. This heterogeneous and multifactorial disease, also known as insulin resistance, is caused by the disruption of the insulin signaling pathway. In this review, we discuss the existence of various miRNAs involved in regulating the main protein cascades in the insulin signaling pathway that affect insulin resistance. The influence of miRNAs (miR-7, miR-124a, miR-9, miR-96, miR-15a/b, miR-34a, miR-195, miR-376, miR-103, miR-107, and miR-146) in insulin secretion and beta (β) cell development has been well discussed. Here, we highlight the role of miRNAs in different significant protein cascades within the insulin signaling pathway such as miR-320, miR-383, miR-181b with IGF-1, and its receptor (IGF1R); miR-128a, miR-96, miR-126 with insulin receptor substrate (IRS) proteins; miR-29, miR-384-5p, miR-1 with phosphatidylinositol 3-kinase (PI3K); miR-143, miR-145, miR-29, miR-383, miR-33a/b miR-21 with AKT/protein kinase B (PKB) and miR-133a/b, miR-223, miR-143 with glucose transporter 4 (GLUT4). Insulin resistance, obesity, and hyperlipidemia (high lipid levels in the blood) have a strong connection with T2D and several miRNAs influence these clinical outcomes such as miR-143, miR-103, and miR-107, miR-29a, and miR-27b. We also corroborate from previous evidence how these interactions are related to insulin resistance and T2D. The insights highlighted in this review will provide a better understanding on the impact of miRNA in the insulin signaling pathway and insulin resistance-associated diagnostics and therapeutics for T2D. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-06-18T07:42:12.200089-05:
      DOI: 10.1002/wrna.1240
       
  • Emerging mechanisms of mRNP remodeling regulation
    • Authors: Chyi-Ying A. Chen; Ann-Bin Shyu
      Pages: n/a - n/a
      Abstract: The assembly and remodeling of the components of messenger ribonucleoprotein particles (mRNPs) are important in determining the fate of a messenger RNA (mRNA). A combination of biochemical and cell biology research, recently complemented by genome-wide high-throughput approaches, has led to significant progress on understanding the formation, dynamics, and function of mRNPs. These studies also advanced the challenging process of identifying the evolving constituents of individual mRNPs at various stages during an mRNA's lifetime. While research on mRNP remodeling in general has been gaining momentum, there has been relatively little attention paid to the regulatory aspect of mRNP remodeling. Here, we discuss the results of some new studies and potential mechanisms for regulation of mRNP remodeling. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-06-12T15:17:50.616899-05:
      DOI: 10.1002/wrna.1241
       
  • Functional repeat‐derived RNAs often originate from
           retrotransposon‐propagated ncRNAs
    • Authors: Katarzyna Matylla‐Kulinska; Hakim Tafer, Adam Weiss, Renée Schroeder
      First page: 591
      Abstract: The human genome is scattered with repetitive sequences, and the ENCODE project revealed that 60–70% of the genomic DNA is transcribed into RNA. As a consequence, the human transcriptome contains a large portion of repeat‐derived RNAs (repRNAs). Here, we present a hypothesis for the evolution of novel functional repeat‐derived RNAs from non‐coding RNAs (ncRNAs) by retrotransposition. Upon amplification, the ncRNAs can diversify in sequence and subsequently evolve new activities, which can result in novel functions. Non‐coding transcripts derived from highly repetitive regions can therefore serve as a reservoir for the evolution of novel functional RNAs. We base our hypothetical model on observations reported for short interspersed nuclear elements derived from 7SL RNA and tRNAs, α satellites derived from snoRNAs and SL RNAs derived from U1 small nuclear RNA. Furthermore, we present novel putative human repeat‐derived ncRNAs obtained by the comparison of the Dfam and Rfam databases, as well as several examples in other species. We hypothesize that novel functional ncRNAs can derive also from other repetitive regions and propose Genomic SELEX as a tool for their identification. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-07-09T13:30:25.838206-05:
      DOI: 10.1002/wrna.1243
       
  • Poly(A) RNA‐binding proteins and polyadenosine RNA: new members and
           novel functions
    • Authors: Callie P. Wigington; Kathryn R. Williams, Michael P. Meers, Gary J. Bassell, Anita H. Corbett
      First page: 601
      Abstract: Poly(A) RNA‐binding proteins (Pabs) bind with high affinity and specificity to polyadenosine RNA. Textbook models show a nuclear Pab, PABPN1, and a cytoplasmic Pab, PABPC, where the nuclear PABPN1 modulates poly(A) tail length and the cytoplasmic PABPC stabilizes poly(A) RNA in the cytoplasm and also enhances translation. While these conventional roles are critically important, the Pab family has expanded recently both in number and in function. A number of novel roles have emerged for both PAPBPN1 and PABPC that contribute to the fine‐tuning of gene expression. Furthermore, as the characterization of the nucleic acid binding properties of RNA‐binding proteins advances, additional proteins that show high affinity and specificity for polyadenosine RNA are being discovered. With this expansion of the Pab family comes a concomitant increase in the potential for Pabs to modulate gene expression. Further complication comes from an expansion of the potential binding sites for Pab proteins as revealed by an analysis of templated polyadenosine stretches present within the transcriptome. Thus, Pabs could influence mRNA fate and function not only by binding to the nontemplated poly(A) tail but also to internal stretches of adenosine. Understanding the diverse functions of Pab proteins is not only critical to understand how gene expression is regulated but also to understand the molecular basis for tissue‐specific diseases that occur when Pab proteins are altered. Here we describe both conventional and recently emerged functions for PABPN1 and PABPC and then introduce and discuss three new Pab family members, ZC3H14, hnRNP‐Q1, and LARP4. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-04-30T12:12:39.288271-05:
      DOI: 10.1002/wrna.1233
       
  • Structure and function of the archaeal exosome
    • Authors: Elena Evguenieva‐Hackenberg; Linlin Hou, Stefanie Glaeser, Gabriele Klug
      First page: 623
      Abstract: The RNA‐degrading exosome in archaea is structurally very similar to the nine‐subunit core of the essential eukaryotic exosome and to bacterial polynucleotide phosphorylase (PNPase). In contrast to the eukaryotic exosome, PNPase and the archaeal exosome exhibit metal ion‐dependent, phosphorolytic activities and synthesize heteropolymeric RNA tails in addition to the exoribonucleolytic RNA degradation in 3′ → 5′ direction. The archaeal nine‐subunit exosome consists of four orthologs of eukaryotic exosomal subunits: the RNase PH‐domain‐containing subunits Rrp41 and Rrp42 form a hexameric ring with three active sites, whereas the S1‐domain‐containing subunits Rrp4 and Csl4 form an RNA‐binding trimeric cap on the top of the ring. In vivo, this cap contains Rrp4 and Csl4 in variable amounts. Rrp4 confers poly(A) specificity to the exosome, whereas Csl4 is involved in the interaction with the archaea‐specific subunit of the complex, the homolog of the bacterial primase DnaG. The archaeal DnaG is a highly conserved protein and its gene is present in all sequenced archaeal genomes, although the exosome was lost in halophilic archaea and some methanogens. In exosome‐containing archaea, DnaG is tightly associated with the exosome. It functions as an additional RNA‐binding subunit with poly(A) specificity in the reconstituted exosome of Sulfolobus solfataricus and enhances the degradation of adenine‐rich transcripts in vitro. Not only the RNA‐binding cap but also the hexameric Rrp41–Rrp42 ring alone shows substrate selectivity and prefers purines over pyrimidines. This implies a coevolution of the exosome and its RNA substrates resulting in 3′‐ends with different affinities to the exosome. WIREs RNA 2014, 5:623–635. doi: 10.1002/wrna.1234 For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-04-30T12:12:35.29816-05:0
      DOI: 10.1002/wrna.1234
       
  • The role of SON in splicing, development, and disease
    • Authors: Xinyi Lu; Huck-Hui Ng, Paula A. Bubulya
      First page: 637
      Abstract: SON is a nuclear protein involved in multiple cellular processes including transcription, pre‐messenger RNA (mRNA) splicing, and cell cycle regulation. Although SON was discovered 25 years ago, the importance of SON's function was only realized recently when its roles in nuclear organization and pre‐mRNA splicing as well as the influence of these activities in maintaining cellular health were unveiled. Furthermore, SON was implicated to have a key role in stem cells as well as during the onset of various diseases such as cancer, influenza, and hepatitis. Here we review the progress that has been made in studying this multifunctional protein and discuss questions that remain to be answered about SON. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-04-30T12:12:41.652491-05:
      DOI: 10.1002/wrna.1235
       
  • Cross talk between spliceosome and microprocessor defines the fate of
           pre‐mRNA
    • Authors: Chiara Mattioli; Giulia Pianigiani, Franco Pagani
      First page: 647
      Abstract: The spliceosome and the microprocessor complex (MPC) are two important processing machineries that act on precursor (pre)‐mRNA. Both cleave the pre‐mRNA to generate spliced mature transcripts and microRNAs (miRNAs), respectively. While spliceosomes identify in a complex manner correct splice sites, MPCs typically target RNA hairpins (pri‐miRNA hairpins). In addition, pre‐mRNA transcripts can contain pri‐miRNA‐like hairpins that are cleaved by the MPC without generating miRNAs. Recent evidence indicates that the position of hairpins on pre‐mRNA, their distance from splice sites, and the relative efficiency of cropping and splicing contribute to determine the fate of a pre‐mRNA. Depending on these factors, a pre‐mRNA can be preferentially used to generate a miRNA, a constitutively or even an alternative spliced transcript. For example, competition between splicing and cropping on splice‐site‐overlapping miRNAs (SO miRNAs) results in alternative spliced isoforms and influences miRNA biogenesis. In several cases, the outcome of a pre‐mRNA transcript and its final handling as miRNA or mRNA substrate can be frequently closely connected to the functional relationships between diverse pre‐mRNA processing events. These events are influenced by both gene context and physiopathological conditions. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-04-30T12:15:31.441572-05:
      DOI: 10.1002/wrna.1236
       
  • DDX6 and its orthologs as modulators of cellular and viral RNA expression
    • Authors: Dirk H. Ostareck; Isabel S. Naarmann-de Vries, Antje Ostareck-Lederer
      First page: 659
      Abstract: DDX6 (Rck/p54), a member of the DEAD‐box family of helicases, is highly conserved from unicellular eukaryotes to vertebrates. Functions of DDX6 and its orthologs in dynamic ribonucleoproteins contribute to global and transcript‐specific messenger RNA (mRNA) storage, translational repression, and decay during development and differentiation in the germline and somatic cells. Its role in pathways that promote mRNA‐specific alternative translation initiation has been shown to be linked to cellular homeostasis, deregulated tissue development, and the control of gene expression in RNA viruses. Recently, DDX6 was found to participate in mRNA regulation mediated by miRNA‐mediated silencing. DDX6 and its orthologs have versatile functions in mRNA metabolism, which characterize them as important post‐transcriptional regulators of gene expression. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-04-30T12:15:28.171356-05:
      DOI: 10.1002/wrna.1237
       
  • Post‐transcriptional regulation in root development
    • Authors: Eva Stauffer; Alexis Maizel
      First page: 679
      Abstract: Plants constantly adapt their root system to the changing environmental conditions. This developmental plasticity is underpinned by changes in the profile of the mRNA expressed. Here we review how post‐transcriptional modulation of gene expression control root development and growth. In particular we focus on the role of small RNA‐mediated post‐transcriptional regulation processes. Small RNAs play an important role in fine tuning gene expression during root formation and patterning, development of lateral organs and symbiosis, nutrient homeostasis, and other stress‐related responses. We also highlight the impact of alternative splicing on root development and the establishment of symbiotic structures as well as the emerging role of long noncoding RNAs in root physiology. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2014-05-14T12:58:57.994758-05:
      DOI: 10.1002/wrna.1239
       
 
 
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