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Journal Cover Wiley Interdisciplinary Reviews : RNA     [SJR: 2.692]   [H-I: 10]
   [3 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Online) 1757-7012
   Published by John Wiley and Sons Homepage  [1605 journals]
  • Computational challenges, tools, and resources for analyzing co‐ and
           post‐transcriptional events in high throughput
    • Authors: Emad Bahrami‐Samani; Dat T. Vo, Patricia Rosa de Araujo, Christine Vogel, Andrew D. Smith, Luiz O. F. Penalva, Philip J. Uren
      Abstract: Co‐ and post‐transcriptional regulation of gene expression is complex and multifaceted, spanning the complete RNA lifecycle from genesis to decay. High‐throughput profiling of the constituent events and processes is achieved through a range of technologies that continue to expand and evolve. Fully leveraging the resulting data is nontrivial, and requires the use of computational methods and tools carefully crafted for specific data sources and often intended to probe particular biological processes. Drawing upon databases of information pre‐compiled by other researchers can further elevate analyses. Within this review, we describe the major co‐ and post‐transcriptional events in the RNA lifecycle that are amenable to high‐throughput profiling. We place specific emphasis on the analysis of the resulting data, in particular the computational tools and resources available, as well as looking toward future challenges that remain to be addressed. 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: 2014-12-16T08:41:34.011111-05:
      DOI: 10.1002/wrna.1274
       
  • ‘Mediator‐ing’ messenger RNA processing
    • Authors: Yan Huang; Xiao Yao, Gang Wang
      Abstract: Pre‐messenger RNA (mRNA) processing, generally including capping, mRNA splicing, and cleavage‐polyadenylation, is physically and functionally associated with transcription. The reciprocal coupling between transcription and mRNA processing ensures the efficient and regulated gene expression and editing. Multiple transcription factors/cofactors and mRNA processing factors are involved in the coupling process. This review focuses on several classic examples and recent advances that enlarge our understanding of how the transcriptional factors or cofactors, especially the Mediator complex, contribute to the RNA Pol II elongation, mRNA splicing, and polyadenylation. 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: 2014-12-16T08:32:00.097932-05:
      DOI: 10.1002/wrna.1273
       
  • Issue information
    • PubDate: 2014-12-14T22:33:07.346759-05:
      DOI: 10.1002/wrna.1275
       
  • Small RNAs with big implications: new insights into H/ACA snoRNA function
           and their role in human disease
    • Authors: Mary McMahon; Adrian Contreras, Davide Ruggero
      Abstract: A myriad of structurally and functionally diverse noncoding RNAs (ncRNAs) have recently been implicated in numerous human diseases including cancer. Small nucleolar RNAs (snoRNAs), the most abundant group of intron‐encoded ncRNAs, are classified into two families (box C/D snoRNAs and box H/ACA snoRNAs) and are required for post‐transcriptional modifications on ribosomal RNA (rRNA). There is now a growing appreciation that nucleotide modifications on rRNA may impart regulatory potential to the ribosome; however, the functional consequence of site‐specific snoRNA‐guided modifications remains poorly defined. Discovered almost 20 years ago, H/ACA snoRNAs are required for the conversion of specific uridine residues to pseudouridine on rRNA. Interestingly, recent reports indicate that the levels of subsets of H/ACA snoRNAs required for pseudouridine modifications at specific sites on rRNA are altered in several diseases, particularly cancer. In this review, we describe recent advances in understanding the downstream consequences of H/ACA snoRNA‐guided modifications on ribosome function, discuss the possible mechanism by which H/ACA snoRNAs may be regulated, and explore prospective expanding functions of H/ACA snoRNAs. Furthermore, we discuss the potential biological implications of alterations in H/ACA snoRNA expression in several human 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: 2014-10-31T13:32:30.900167-05:
      DOI: 10.1002/wrna.1266
       
  • An introduction to recurrent nucleotide interactions in RNA
    • Authors: Blake A. Sweeney; Poorna Roy, Neocles B. Leontis
      Pages: n/a - n/a
      Abstract: RNA secondary structure diagrams familiar to molecular biologists summarize at a glance the folding of RNA chains to form Watson–Crick paired double helices. However, they can be misleading: First of all, they imply that the nucleotides in loops and linker segments, which can amount to 35% to 50% of a structured RNA, do not significantly interact with other nucleotides. Secondly, they give the impression that RNA molecules are loosely organized in three‐dimensional (3D) space. In fact, structured RNAs are compactly folded as a result of numerous long‐range, sequence‐specific interactions, many of which involve loop or linker nucleotides. Here, we provide an introduction for students and researchers of RNA on the types, prevalence, and sequence variations of inter‐nucleotide interactions that structure and stabilize RNA 3D motifs and architectures, using Escherichia coli (E. coli) 16S ribosomal RNA as a concrete example. The picture that emerges is that almost all nucleotides in structured RNA molecules, including those in nominally single‐stranded loop or linker regions, form specific interactions that stabilize functional structures or mediate interactions with other molecules. The small number of noninteracting, ‘looped‐out’ nucleotides make it possible for the RNA chain to form sharp turns. Base‐pairing is the most specific interaction in RNA as it involves edge‐to‐edge hydrogen bonding (H‐bonding) of the bases. Non‐Watson–Crick base pairs are a significant fraction (30% or more) of base pairs in structured RNAs. 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: 2014-10-29T13:18:19.21524-05:0
      DOI: 10.1002/wrna.1258
       
  • Understanding the potential of hepatitis C virus internal ribosome entry
           site domains to modulate translation initiation via their structure and
           function
    • Authors: Anas Khawaja; Vaclav Vopalensky, Martin Pospisek
      Pages: n/a - n/a
      Abstract: Translation initiation in the hepatitis C virus (HCV) occurs through a cap‐independent mechanism that involves an internal ribosome entry site (IRES) capable of interacting with and utilizing the eukaryotic translational machinery. In this review, we focus on the structural configuration of the different HCV IRES domains and the impact of IRES primary sequence variations on secondary structure conservation and function. In some cases, multiple mutations, even those scattered across different domains, led to restoration of the translational activity of the HCV IRES, although the individual occurrences of these mutations were found to be deleterious. We propose that such observation may be attributed to probable long‐range inter‐ and/or intra‐domain functional interactions. The precise functioning of the HCV IRES requires the specific interaction of its domains with ribosomal subunits and a subset of eukaryotic translation initiation factors (eIFs). The structural conformation, sequence preservation and variability, and translational machinery association with the HCV IRES regions are also thoroughly discussed, along with other factors that can affect and influence the formation of translation initiation complexes. 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: 2014-10-28T10:03:16.737631-05:
      DOI: 10.1002/wrna.1268
       
  • An overview of pre‐ribosomal RNA processing in eukaryotes
    • Authors: Anthony K. Henras; Célia Plisson‐Chastang, Marie‐Françoise O'Donohue, Anirban Chakraborty, Pierre‐Emmanuel Gleizes
      Pages: n/a - n/a
      Abstract: Ribosomal RNAs are the most abundant and universal noncoding RNAs in living organisms. In eukaryotes, three of the four ribosomal RNAs forming the 40S and 60S subunits are borne by a long polycistronic pre‐ribosomal RNA. A complex sequence of processing steps is required to gradually release the mature RNAs from this precursor, concomitant with the assembly of the 79 ribosomal proteins. A large set of trans‐acting factors chaperone this process, including small nucleolar ribonucleoparticles. While yeast has been the gold standard for studying the molecular basis of this process, recent technical advances have allowed to further define the mechanisms of ribosome biogenesis in animals and plants. This renewed interest for a long‐lasting question has been fueled by the association of several genetic diseases with mutations in genes encoding both ribosomal proteins and ribosome biogenesis factors, and by the perspective of new anticancer treatments targeting the mechanisms of ribosome synthesis. A consensus scheme of pre‐ribosomal RNA maturation is emerging from studies in various kinds of eukaryotic organisms. However, major differences between mammalian and yeast pre‐ribosomal RNA processing have recently come to light. 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: 2014-10-27T01:11:44.674174-05:
      DOI: 10.1002/wrna.1269
       
  • Processing of preribosomal RNA in Saccharomyces cerevisiae
    • Authors: Antonio Fernández‐Pevida; Dieter Kressler, Jesús de la Cruz
      Abstract: Most, if not all RNAs, are transcribed as precursors that require processing to gain functionality. Ribosomal RNAs (rRNA) from all organisms undergo both exo‐ and endonucleolytic processing. Also, in all organisms, rRNA processing occurs inside large preribosomal particles and is coupled to nucleotide modification, folding of the precursor rRNA (pre‐rRNA), and assembly of the ribosomal proteins (r‐proteins). In this review, we focus on the processing pathway of pre‐rRNAs of cytoplasmic ribosomes in the yeast Saccharomyces cerevisiae, without doubt, the organism where this pathway is best characterized. We summarize the current understanding of the rRNA maturation process, particularly focusing on the pre‐rRNA processing sites, the enzymes responsible for the cleavage or trimming reactions and the different mechanisms that monitor and regulate the pathway. Strikingly, the overall order of the various processing steps is reasonably well conserved in eukaryotes, perhaps reflecting common principles for orchestrating the concomitant events of pre‐rRNA processing and ribosome assembly. 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: 2014-10-18T05:01:30.990362-05:
      DOI: 10.1002/wrna.1267
       
  • Ilf3 and NF90 functions in RNA biology
    • Authors: Sandrine Castella; Rozenn Bernard, Mélanie Corno, Aurélie Fradin, Jean‐Christophe Larcher
      Abstract: Double‐stranded RNA‐binding proteins (DRBPs) are known to regulate many processes of RNA metabolism due, among others, to the presence of double‐stranded RNA (dsRNA)‐binding motifs (dsRBMs). Among these DRBPs, Interleukin enhancer‐binding factor 3 (Ilf3) and Nuclear Factor 90 (NF90) are two ubiquitous proteins generated by mutually exclusive and alternative splicings of the Ilf3 gene. They share common N‐terminal and central sequences but display specific C‐terminal regions. They present a large heterogeneity generated by several post‐transcriptional and post‐translational modifications involved in their subcellular localization and biological functions. While Ilf3 and NF90 were first identified as activators of gene expression, they are also implicated in cellular processes unrelated to RNA metabolism such as regulation of the cell cycle or of enzymatic activites. The implication of Ilf3 and NF90 in RNA biology will be discussed with a focus on eukaryote transcription and translation regulation, on viral replication and translation as well as on noncoding RNA field. 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: 2014-10-18T04:58:52.572364-05:
      DOI: 10.1002/wrna.1270
       
  • Effects of messenger RNA structure and other translational control
           mechanisms on major histocompatibility complex‐I mediated antigen
           presentation
    • Authors: Pierre Murat; Judy Tellam
      Abstract: Effective T‐cell surveillance of antigen‐presenting cells is dependent on the expression of an array of antigenic peptides bound to major histocompatibility complex (MHC) class I (MHC‐I) or class II (MHC‐II) molecules. Pathogens co‐evolving with their hosts exploit crucial translational regulatory mechanisms in order to evade host immune recognition and thereby sustain their infection. Evasion strategies that downregulate viral protein synthesis and thereby restrict antigen presentation to cytotoxic T‐cells through the endogenous MHC‐I pathway have been implicated in the pathogenesis of viral‐associated malignancies. An understanding of the mechanisms by which messenger RNA (mRNA) structure modulates both viral mRNA translation and the antigen processing machinery to escape immune surveillance, will stimulate the development of alternative therapeutic strategies focused on RNA‐directed drugs designed to enhance immune responses against infected cells. In this review, we discuss regulatory aspects of the MHC‐I pathway and summarize current knowledge of the role attributed by mRNA structure and other translational regulatory mechanisms in immune evasion. In particular we highlight the impact of recently identified G‐quadruplex structures within virally encoded transcripts as unique regulatory signals for translational control and antigen presentation. 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: 2014-09-26T10:07:27.094592-05:
      DOI: 10.1002/wrna.1262
       
  • 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
       
  • Control of cell migration through mRNA localization and local translation
    • Authors: Guoning Liao; Lisa Mingle, Livingston Van De Water, Gang Liu
      First page: 1
      Abstract: Cell migration plays an important role in many normal and pathological functions such as development, wound healing, immune defense, and tumor metastasis. Polarized migrating cells exhibit asymmetric distribution of many cytoskeletal proteins, which is believed to be critical for establishing and maintaining cell polarity and directional cell migration. To target these proteins to the site of function, cells use a variety of mechanisms such as protein transport and messenger RNA (mRNA) localization‐mediated local protein synthesis. In contrast to the former which is intensively investigated and relatively well understood, the latter has been understudied and relatively poorly understood. However, recent advances in the study of mRNA localization and local translation have demonstrated that mRNA localization and local translation are specific and effective ways for protein localization and are crucial for embryo development, neuronal function, and many other cellular processes. There are excellent reviews on mRNA localization, transport, and translation during development and other cellular processes. This review will focus on mRNA localization‐mediated local protein biogenesis and its impact on somatic cell migration. 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: 2014-09-28T17:58:27.270557-05:
      DOI: 10.1002/wrna.1265
       
  • CLP1 as a novel player in linking tRNA splicing to neurodegenerative
           disorders
    • Authors: Stefan Weitzer; Toshikatsu Hanada, Josef M. Penninger, Javier Martinez
      First page: 47
      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
       
  • Insights into the U1 small nuclear ribonucleoprotein complex superfamily
    • Authors: J Guiro; D O'Reilly
      First page: 79
      Abstract: The 164 bp U1 small nuclear (sn) RNA is one of the most abundant noncoding (nc) RNA in human cells, estimated to be in the region of 106 copies/cell. Although best known for its role in pre‐messenger RNA (mRNA) splicing events, research over the past 20 years has revealed diverse functions of this ncRNA in mammalian cell types. Excellent reviews exist detailing the role of U1 snRNA in pre‐mRNA splicing events. This review highlights what is currently known regarding the additional roles, snRNP composition, expression profiles, and the genomic organization of this ncRNA. 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: 2014-09-26T07:38:13.331379-05:
      DOI: 10.1002/wrna.1257
       
  • The RNAissance family: SR proteins as multifaceted regulators of gene
           expression
    • Authors: Jonathan M. Howard; Jeremy R. Sanford
      First page: 93
      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
      First page: 111
      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
       
  • Cotranscriptional events in eukaryotic ribosome synthesis
    • Authors: Tomasz W. Turowski; David Tollervey
      First page: 129
      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 influence of Argonaute proteins on alternative RNA splicing
    • Authors: Eric Batsché; Maya Ameyar‐Zazoua
      First page: 141
      Abstract: Alternative splicing of precursor RNAs is an important process in multicellular species because it impacts several aspects of gene expression: from the increase of protein repertoire to the level of expression. A large body of evidences demonstrates that factors regulating chromatin and transcription impact the outcomes of alternative splicing. Argonaute (AGO) proteins were known to play key roles in the regulation of gene expression at the post‐transcriptional level. More recently, their role in the nucleus of human somatic cells has emerged. Here, we will discuss some of the nuclear functions of AGO, with special emphasis on alternative splicing. The AGO‐mediated modulation of alternative splicing is based on several properties of these proteins: their binding to transcripts on chromatin and their interactions with many proteins, especially histone tail‐modifying enzymes, HP1γ and splicing factors. AGO proteins may favor a decrease in the RNA‐polymerase II kinetics at actively transcribed genes leading to the modulation of alternative splicing decisions. They could also influence alternative splicing through their interaction with core components of the splicing machinery and several splicing factors. We will discuss the modes of AGO recruitment on chromatin at active genes. We suggest that long intragenic antisense transcripts (lincRNA) might be an important feature of genes containing splicing events regulated by AGO. 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: 2014-09-25T14:12:37.715526-05:
      DOI: 10.1002/wrna.1264
       
 
 
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