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Journal Cover Wiley Interdisciplinary Reviews : RNA
   [3 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Online) 1757-7012
     Published by John Wiley and Sons Homepage  [1602 journals]   [SJR: 2.692]   [H-I: 10]
  • 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
  • Issue information
    • Pages: no - no
      PubDate: 2014-06-16T11:32:37.260197-05:
      DOI: 10.1002/wrna.1251
  • 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
  • Post‐transcriptional regulation in root development
    • Authors: Eva Stauffer; Alexis Maizel
      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
  • Cross talk between spliceosome and microprocessor defines the fate of
    • Authors: Chiara Mattioli; Giulia Pianigiani, Franco Pagani
      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
      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
  • The role of SON in splicing, development, and disease
    • Authors: Xinyi Lu; Huck-Hui Ng, Paula A. Bubulya
      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
  • 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
      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
      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. 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
  • Splicing factor mutations and cancer
    • Authors: Kenichi Yoshida; Seishi Ogawa
      First page: 445
      Abstract: Recent advances in high‐throughput sequencing technologies have unexpectedly revealed that somatic mutations of splicing factor genes frequently occurred in several types of hematological malignancies, including myelodysplastic syndromes, other myeloid neoplasms, and chronic lymphocytic leukemia. Splicing factor mutations have also been reported in solid cancers such as breast and pancreatic cancers, uveal melanomas, and lung adenocarcinomas. These mutations were heterozygous and mainly affected U2AF1 (U2AF35), SRSF2 (SC35), SF3B1 (SF3B155 or SAP155), and ZRSR2 (URP), which are engaged in the initial steps of RNA splicing, including 3′ splice‐site recognition, and occur in a large mutually exclusive pattern, suggesting a common impact of these mutations on RNA splicing. In this study, splicing factor mutations in various types of cancers, their functional/biological effects, and their potential as therapeutic targets have been reviewed. 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: 2014-02-12T13:43:45.094562-05:
      DOI: 10.1002/wrna.1222
  • tRNA synthetase: tRNA aminoacylation and beyond
    • Authors: Yan Ling Joy Pang; Kiranmai Poruri, Susan A. Martinis
      First page: 461
      Abstract: The aminoacyl‐tRNA synthetases are prominently known for their classic function in the first step of protein synthesis, where they bear the responsibility of setting the genetic code. Each enzyme is exquisitely adapted to covalently link a single standard amino acid to its cognate set of tRNA isoacceptors. These ancient enzymes have evolved idiosyncratically to host alternate activities that go far beyond their aminoacylation role and impact a wide range of other metabolic pathways and cell signaling processes. The family of aminoacyl‐tRNA synthetases has also been suggested as a remarkable scaffold to incorporate new domains that would drive evolution and the emergence of new organisms with more complex function. Because they are essential, the tRNA synthetases have served as pharmaceutical targets for drug and antibiotic development. The recent unfolding of novel important functions for this family of proteins offers new and promising pathways for therapeutic development to treat diverse 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: 2014-04-04T08:12:26.658694-05:
      DOI: 10.1002/wrna.1224
  • Localization of mRNAs to the endoplasmic reticulum
    • Authors: Xianying A. Cui; Alexander F. Palazzo
      First page: 481
      Abstract: Almost all cells use mRNA localization to establish spatial control of protein synthesis. One of the best‐studied examples is the targeting and anchoring of mRNAs encoding secreted, organellar, and membrane‐bound proteins to the surface of the endoplasmic reticulum (ER). In this review, we provide a historical perspective on the research that elucidated the canonical protein‐mediated targeting of nascent‐chain ribosome mRNA complexes to the surface of the ER. We then discuss subsequent studies which provided concrete evidence that a subpopulation of mRNAs utilize a translation‐independent mechanism to localize to the surface of this organelle. This alternative mechanism operates alongside the signal recognition particle (SRP) mediated co‐translational targeting pathway to promote proper mRNA localization to the ER. Recent work has uncovered trans‐acting factors, such as the mRNA receptor p180, and cis‐acting elements, such as transmembrane domain coding regions, that are responsible for this alternative mRNA localization process. Furthermore, some unanticipated observations have raised the possibility that this alternative pathway may be conserved from bacteria to mammalian cells. 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: 2014-03-18T08:56:19.77196-05:0
      DOI: 10.1002/wrna.1225
  • The multifaceted roles of RNA binding in APOBEC cytidine deaminase
    • Authors: Kimberly M. Prohaska; Ryan P. Bennett, Jason D. Salter, Harold C. Smith
      First page: 493
      Abstract: Cytidine deaminases have important roles in the regulation of nucleoside/deoxynucleoside pools for DNA and RNA synthesis. The APOBEC family of cytidine deaminases (named after the first member of the family that was described, Apolipoprotein B mRNA Editing Catalytic Subunit 1, also known as APOBEC1 or A1) is a fascinating group of mutagenic proteins that use RNA and single‐stranded DNA (ssDNA) as substrates for their cytidine or deoxycytidine deaminase activities. APOBEC proteins and base‐modification nucleic acid editing have been the subject of numerous publications, reviews, and speculation. These proteins play diverse roles in host cell defense, protecting cells from invading genetic material, enabling the acquired immune response to antigens and changing protein expression at the level of the genetic code in mRNA or DNA. The amazing power these proteins have for interphase cell functions relies on structural and biochemical properties that are beginning to be understood. At the same time, the substrate selectivity of each member in the family and their regulation remains to be elucidated. This review of the APOBEC family will focus on an open question in regulation, namely what role the interactions of these proteins with RNA have in editing substrate recognition or allosteric regulation of DNA mutagenic and host‐defense activities. For further resources related to this article, please visit the WIREs website. Conflict of interest: KMP, RPB, and JDS are employees of OyaGen Inc, which is a drug development biotechnology company engaged in the therapeutic targeting of editing enzymes. Dr. Smith is the founder of OyaGen and, as a consultant, serves as CEO and CSO for OyaGen. Dr. Smith is a tenured full professor in the Department of Biochemistry and Biophysics, Center for RNA Biology and Cancer Center at the University of Rochester, School of Medicine and Dentistry in Rochester, NY.
      PubDate: 2014-03-24T14:13:52.787989-05:
      DOI: 10.1002/wrna.1226
  • MicroRNA in skeletal muscle development, growth, atrophy, and disease
    • Authors: Anja Kovanda; Tadeja Režen, Boris Rogelj
      First page: 509
      Abstract: MicroRNAs (miRNAs) are short noncoding RNAs that are important global‐ as well as tissue‐ and cell‐type‐specific regulators of gene expression. Muscle‐specific miRNAs or myomirs have been shown to control various processes in skeletal muscles, from myogenesis and muscle homeostasis to different responses to environmental stimuli, such as exercise. Importantly, myomirs are also involved in the development of muscle atrophy arising from aging, immobility, prolonged exposure to microgravity, or muscular and neuromuscular disorders. Additionally, muscle atrophy is both induced by and exacerbates many important chronic and infectious diseases. As global yet specific muscle regulators, myomirs are also good candidates for therapeutic use. Understanding the dynamics of myomirs expression and their role in the development of disease is necessary to determine their potential for muscle atrophy prevention. For further resources related to this article, please visit the WIREs website. The authors declare no conflicts of interest.
      PubDate: 2014-05-16T06:59:03.673027-05:
      DOI: 10.1002/wrna.1227
  • The roles of DAZL in RNA biology and development
    • Authors: Lukasz Smorag; Xingbo Xu, Wolfgang Engel, D.V. Krishna Pantakani
      First page: 527
      Abstract: RNA‐binding proteins play an important role in the regulation of gene expression by modulating translation and localization of specific messenger RNAs (mRNAs) during early development and gametogenesis. The DAZ (Deleted in Azoospermia) family of proteins, which includes DAZ, DAZL, and BOULE, are germ cell‐specific RNA‐binding proteins that are implicated in translational regulation of several transcripts. Of particular importance is DAZL, which is present in vertebrates and arose from the duplication of the ancestral BOULE during evolution. Identification of DAZL target mRNAs and characterization of the RNA‐binding sequence through in vitro binding assays and crystallographic studies revealed that DAZL binds to GUU triplets in the 3′ untranslated region of target mRNAs. Although there is compelling evidence for the role of DAZL in translation stimulation of target mRNAs, recent studies indicate that DAZL can also function in translational repression and transport of specific mRNAs. Furthermore, apart from the well‐characterized function of DAZL in gametogenesis, recent data suggest its role in early embryonic development and differentiation of pluripotent stem cells toward functional gametes. In light of the mounting evidence for the role of DAZL in various cellular and developmental processes, we summarize the currently characterized biological functions of DAZL in RNA biology and development. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors declare no potential conflict of interest.
      PubDate: 2014-04-08T19:21:47.441441-05:
      DOI: 10.1002/wrna.1228
  • MicroRNAs as therapeutic targets in human cancers
    • Authors: Maitri Y. Shah; George A. Calin
      First page: 537
      Abstract: MicroRNAs (miRNAs) are evolutionarily conserved, small, regulatory RNAs that negatively regulate gene expression. Extensive research in the last decade has implicated miRNAs as master regulators of cellular processes with essential role in cancer initiation, progression, and metastasis, making them promising therapeutic tools for cancer management. In this article, we will briefly review the structure, biogenesis, functions, and mechanism of action of these miRNAs, followed by a detailed analysis of the therapeutic potential of these miRNAs. We will focus on the strategies presently used for miRNA therapy; discuss their use and drawbacks; and the challenges and future directions for the development of miRNA‐based therapy for human cancers. 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: 2014-03-28T15:03:21.068444-05:
      DOI: 10.1002/wrna.1229
  • Physiological networks and disease functions of RNA‐binding protein
    • Authors: Ashleigh E. Moore; Devon M. Chenette, Lauren C. Larkin, Robert J. Schneider
      First page: 549
      Abstract: Regulated messenger RNA (mRNA) decay is an essential mechanism that governs proper control of gene expression. In fact, many of the most physiologically potent proteins are encoded by short‐lived mRNAs, many of which contain AU‐rich elements (AREs) in their 3′‐untranslated region (3′‐UTR). AREs target mRNAs for post‐transcriptional regulation, generally rapid decay, but also stabilization and translation inhibition. AREs control mRNA turnover and translation activities through association with trans‐acting RNA‐binding proteins that display high affinity for these AU‐rich regulatory elements. AU‐rich element RNA‐binding protein (AUF1), also known as heterogeneous nuclear ribonucleoprotein D (HNRNPD), is an extensively studied AU‐rich binding protein (AUBP). AUF1 has been shown to regulate ARE‐mRNA turnover, primarily functioning to promote rapid ARE‐mRNA degradation. In certain cellular contexts, AUF1 has also been shown to regulate gene expression at the translational and even the transcriptional level. AUF1 comprises a family of four related protein isoforms derived from a common pre‐mRNA by differential exon splicing. AUF1 isoforms have been shown to display multiple and distinct functions that include the ability to target ARE‐mRNA stability or decay, and transcriptional activation of certain genes that is controlled by their differential subcellular locations, expression levels, and post‐translational modifications. AUF1 has been implicated in controlling a variety of physiological functions through its ability to regulate the expression of numerous mRNAs containing 3′‐UTR AREs, thereby coordinating functionally related pathways. This review highlights the physiological functions of AUF1‐mediated regulation of mRNA and gene expression, and the consequences of deficient AUF1 levels in different physiological 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: 2014-03-28T15:03:23.247417-05:
      DOI: 10.1002/wrna.1230
  • Neuronal RNA‐binding proteins in health and disease
    • Authors: Silvia Carolina Lenzken; Tilmann Achsel, Maria Teresa Carrì, Silvia M.L. Barabino
      First page: 565
      Abstract: In mammalian cells in general and in neurons in particular, mRNA maturation, translation, and degradation are highly complex and dynamic processes. RNA‐binding proteins (RBPs) play crucial roles in all these events. First, they participate in the choice of pre‐mRNA splice sites and in the selection of the polyadenylation sites, determining which of the possible isoforms is produced from a given precursor mRNA. Then, once in the cytoplasm, the protein composition of the RNP particles determines whether the mature mRNA is transported along the dendrites or the axon of a neuron to the synapses, how efficiently it is translated, and how stable it is. In agreement with their importance for neuronal function, mutations in genes that code for RBPs are associated with various neurological diseases. In this review, we illustrate how individual RBPs determine the fate of an mRNA, and we discuss how mutations in RBPs or perturbations of the mRNA metabolism can cause neurodegenerative disorders. 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: 2014-03-28T15:04:53.890635-05:
      DOI: 10.1002/wrna.1231
  • Degradation of oligouridylated histone mRNAs: see UUUUU and goodbye
    • Authors: Kai P. Hoefig; Vigo Heissmeyer
      First page: 577
      Abstract: During the cell cycle the expression of replication‐dependent histones is tightly coupled to DNA synthesis. Histone messenger RNA (mRNA) levels strongly increase during early S‐phase and rapidly decrease at the end of it. Here, we review the degradation of replication‐dependent histone mRNAs, a paradigm of post‐transcriptional gene regulation, in the context of processing, translation, and oligouridylation. Replication‐dependent histone transcripts are characterized by the absence of introns and by the presence of a stem‐loop structure at the 3′ end of a very short 3′ untranslated region (UTR). These features, together with a need for active translation, are a prerequisite for their rapid decay. The degradation is induced by 3′ end additions of untemplated uridines, performed by terminal uridyl transferases. Such 3′ oligouridylated transcripts are preferentially bound by the heteroheptameric LSM1‐7 complex, which also interacts with the 3′→5′ exonuclease ERI1 (also called 3′hExo). Presumably in cooperation with LSM1‐7 and aided by the helicase UPF1, ERI1 degrades through the stem‐loop of oligouridylated histone mRNAs in repeated rounds of partial degradation and reoligouridylation. Although histone mRNA decay is now known in some detail, important questions remain open: How is ceasing nuclear DNA replication relayed to the cytoplasmic histone mRNA degradation' Why is translation important for this process' Recent research on factors such as SLIP1, DBP5, eIF3, CTIF, CBP80/20, and ERI1 has provided new insights into the 3′ end formation, the nuclear export, and the translation of histone mRNAs. We discuss how these results fit with the preparation of histone mRNAs for degradation, which starts as early as these transcripts are generated. 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: 2014-04-01T09:26:18.947896-05:
      DOI: 10.1002/wrna.1232
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