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Journal Cover Wiley Interdisciplinary Reviews : RNA
  [SJR: 4.563]   [H-I: 36]   [3 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Online) 1757-7012
   Published by John Wiley and Sons Homepage  [1577 journals]
  • Insights into RNA structure and dynamics from recent NMR and X-ray studies
           of the Neurospora Varkud satellite ribozyme
    • Authors: Pierre Dagenais; Nicolas Girard, Eric Bonneau, Pascale Legault
      Abstract: Despite the large number of noncoding RNAs and their importance in several biological processes, our understanding of RNA structure and dynamics at atomic resolution is still very limited. Like many other RNAs, the Neurospora Varkud satellite (VS) ribozyme performs its functions through dynamic exchange of multiple conformational states. More specifically, the VS ribozyme recognizes and cleaves its stem-loop substrate via a mechanism that involves several structural transitions within its stem-loop substrate. The recent publications of high-resolution structures of the VS ribozyme, obtained by NMR spectroscopy and X-ray crystallography, offer an opportunity to integrate the data and closely examine the structural and dynamic properties of this model RNA system. Notably, these investigations provide a valuable example of the divide-and-conquer strategy for structural and dynamic characterization of a large RNA, based on NMR structures of several individual subdomains. The success of this divide-and-conquer approach reflects the modularity of RNA architecture and the great care taken in identifying the independently-folding modules. Together with previous biochemical and biophysical characterizations, the recent NMR and X-ray studies provide a coherent picture into how the VS ribozyme recognizes its stem-loop substrate. Such in-depth characterization of this RNA enzyme will serve as a model for future structural and engineering studies of dynamic RNAs and may be particularly useful in planning divide-and-conquer investigations.For further resources related to this article, please visit the WIREs website.Recent structural studies provide an atomic view of substrate recognition and cleavage by the VS ribozyme.
      PubDate: 2017-04-06T03:58:34.22102-05:0
      DOI: 10.1002/wrna.1421
       
  • Functional diversity of Arabidopsis organelle-localized RNA-recognition
           motif-containing proteins
    • Authors: Xiaowen Shi; Maureen R. Hanson, Stephane Bentolila
      Abstract: RNA-Binding Proteins (RBPs) play key roles in plant gene expression and regulation. RBPs contain a variety of RNA-binding motifs, the most abundant and most widespread one in eukaryotes is the RNA recognition motif (RRM). Many nucleus-encoded RRM-containing proteins are transported into chloroplasts and/or mitochondria, and participate in various RNA-related processes in plant organelles. Loss of these proteins can have a detrimental effect on some critical processes such as photosynthesis and respiration, sometimes leading to lethality. Progress has been made in the last few years in understanding the function of particular organelle-localized RRM-containing proteins. Members of the Organelle RRM protein (ORRM, some also characterized as Glycine-Rich RNA-Binding Proteins) family and the Chloroplast RiboNucleoProtein (cpRNP) family, are involved in various types of RNA metabolism, including RNA editing, RNA stability and RNA processing. Organelle-localized RRM proteins also function in plant development and stress responses, in some conditions acting as protein or RNA chaperones. There has been recent progress in characterizing the function of organelle-localized RRM proteins in RNA-related processes and how RRM proteins contribute to the normal growth and development of plants.For further resources related to this article, please visit the WIREs website.Organelle-localized RRM proteins participate in a variety of RNA-related processes, which consequently alters expression of many genes. Many organelle-localized RRM proteins are also involved in plant stress response and/or plant development. However, the association between these processes still awaits investigation.
      PubDate: 2017-03-29T21:45:30.678635-05:
      DOI: 10.1002/wrna.1420
       
  • Box C/D small nucleolar RNA genes and the Prader-Willi syndrome: a complex
           interplay
    • Authors: Jérôme Cavaillé
      Abstract: The nucleolus of mammalian cells contains hundreds of box C/D small nucleolar RNAs (SNORDs). Through their ability to base pair with ribosomal RNA precursors, most play important roles in the synthesis and/or activity of ribosomes, either by guiding sequence-specific 2′-O-methylations or by facilitating RNA folding and cleavages. A growing number of SNORD genes with elusive functions have been discovered recently. Intriguingly, the vast majority of them are located in two large, imprinted gene clusters at human chromosome region 15q11q13 (the SNURF–SNRPN domain) and at 14q32 (the DLK1–DIO3 domain) where they are expressed, respectively, only from the paternally and maternally inherited alleles. These placental mammal-specific SNORD genes have many features of the canonical SNORDs that guide 2′-O-methylations, yet they lack obvious complementarity with ribosomal RNAs and, surprisingly, they are processed from large, tandemly repeated genes expressed preferentially in the brain. This review summarizes our understanding of the biology of these peculiar SNORD genes, focusing particularly on SNORD115 and SNORD116 in the SNURF–SNRPN domain. It examines the growing evidence that altered levels of these SNORDs and/or their host-gene transcripts may be a primary cause of Prader-Willi syndrome (PWS; a rare disorder characterized by overeating and obesity) as well as abnormalities in signaling through the 5-HT2C serotonin receptor. Finally, the hypothesis that PWS may be a ribosomopathy (ribosomal disease) is also discussed.For further resources related to this article, please visit the WIREs website.The imprinted gene cluster at 15q11q13.
      PubDate: 2017-03-13T21:10:37.832566-05:
      DOI: 10.1002/wrna.1417
       
  • Cell cycle RNA regulons coordinating early lymphocyte development
    • Authors: Alison Galloway; Martin Turner
      Abstract: Lymphocytes undergo dynamic changes in gene expression as they develop from progenitor cells lacking antigen receptors, to mature cells that are prepared to mount immune responses. While transcription factors have established roles in lymphocyte development, they act in concert with post-transcriptional and post-translational regulators to determine the proteome. Furthermore, the post-transcriptional regulation of RNA regulons consisting of mRNAs whose protein products act cooperatively allows RNA binding proteins to exert their effects at multiple points in a pathway. Here, we review recent evidence demonstrating the importance of RNA binding proteins that control the cell cycle in lymphocyte development and discuss the implications for tumorigenesis.For further resources related to this article, please visit the WIREs website.RNA binding proteins influence the expression of cell cycle regulators, which then in turn affects the balance of cell cycle progression and V(D)J recombination in developing lymphocytes. In this review, we discuss how RNA binding protein (RBP) regulates the cell cycle and other pathways in developing lymphocytes.
      PubDate: 2017-02-23T19:35:27.697468-05:
      DOI: 10.1002/wrna.1419
       
  • Microexons: discovery, regulation, and function
    • Authors: Dmytro Ustianenko; Sebastien M. Weyn-Vanhentenryck, Chaolin Zhang
      Abstract: The importance of RNA splicing in numerous cellular processes is well established. However, an underappreciated aspect is the ability of the spliceosome to recognize a set of very small (3–30 nucleotide, 1–10 amino acid) exons named microexons. Despite their small size, microexons and their regulation through alternative splicing have now been shown to play critical roles in protein and system function. Here we review the discovery of microexons over time and the mechanisms by which their splicing is regulated, including recent progress made through deep RNA sequencing. We also discuss the functional role of microexons in biology and disease.For further resources related to this article, please visit the WIREs website.A snapshot of microexon regulation and their ability to modulate protein properties, including mechanistic links to disease.
      PubDate: 2017-02-11T02:30:28.448862-05:
      DOI: 10.1002/wrna.1418
       
  • RNA in extracellular vesicles
    • Authors: Kyoung Mi Kim; Kotb Abdelmohsen, Maja Mustapic, Dimitrios Kapogiannis, Myriam Gorospe
      Abstract: Cells release a range of membrane-enclosed extracellular vesicles (EVs) into the environment. Among them, exosomes and microvesicles (collectively measuring 40–1000 nm in diameter) carry proteins, signaling lipids, and nucleic acids from donor cells to recipient cells, and thus have been proposed to serve as intercellular mediators of communication. EVs transport cellular materials in many physiologic processes, including differentiation, stem cell homeostasis, immune responses, and neuronal signaling. EVs are also increasingly recognized as having a direct role in pathologies such as cancer and neurodegeneration. Accordingly, EVs have been the focus of intense investigation as biomarkers of disease, prognostic indicators, and even therapeutic tools. Here, we review the classes of RNAs present in EVs, both coding RNAs (messenger RNAs) and noncoding RNAs (long noncoding RNAs, microRNAs, and circular RNAs). The rising attention to EV-resident RNAs as biomarkers stems from the fact that RNAs can be detected at extremely low quantities using a number of methods. To illustrate the interest in EV biology, we discuss EV RNAs in cancer and neurodegeneration, two major age-associated disease processes.For further resources related to this article, please visit the WIREs website.Extracellular vesicles (EVs) contain different RNA species, including messenger RNAs (mRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and Circular RNAs (cirRNAs). These cargo RNAs may affect gene expression patterns in recipient cells and/or serve as diagnostic and prognostic markers.
      PubDate: 2017-01-28T03:15:37.47873-05:0
      DOI: 10.1002/wrna.1413
       
  • microRNA-binding proteins: specificity and function
    • Authors: Richard W. Zealy; Samuel P. Wrenn, Sylvia Davila, Kyung-Won Min, Je-Hyun Yoon
      Abstract: microRNA (miRNA) and RNA-binding proteins (RBPs) have been studied widely in post-transcriptional gene regulation. Previous work has focused on defining how miRNA and RBPs modulate target mRNA decay and translation as well as investigating how they interplay each other. Emerging studies indicate that certain RBPs other than the AGO-family proteins directly interact with mature miRNAs. These findings implicate competitive binding of RBPs to target miRNAs, sequestration of miRNAs from AGO, promotion of AGO binding to miRNAs, and transfer of miRNAs from RBPs to AGO. Recent work also indicates that AGO-free cytoplasmic miRNAs establish complexes with novel miRNA-binding proteins (miRBPs). This review covers the recent discovery of novel miRBPs, offering a new perspective on the miRNA-mediated gene silencing mechanism.For further resources related to this article, please visit the WIREs website.miRNA-binding proteins (miRBPs) cooperate or compete with AGO2 for miRNA binding in miRNA-mediated gene silencing.
      PubDate: 2017-01-28T02:35:30.731682-05:
      DOI: 10.1002/wrna.1414
       
  • Structures of RNA repeats associated with neurological diseases
    • Authors: Leszek Błaszczyk; Wojciech Rypniewski, Agnieszka Kiliszek
      Abstract: All RNA molecules possess a ‘propensity’ to fold into complex secondary and tertiary structures. Although they are composed of only four types of nucleotides, they show an enormous structural richness which reflects their diverse functions in the cell. However, in some cases the folding of RNA can have deleterious consequences. Aberrantly expanded, repeated RNA sequences can exhibit gain-of-function abnormalities and become pathogenic, giving rise to many incurable neurological diseases. Most RNA repeats form long hairpin structures whose stem consists of noncanonical base pairs interspersed among Watson–Crick pairs. The expanded hairpins have an ability to sequester important proteins and form insoluble nuclear foci. The RNA pathology, common to many repeat disorders, has drawn attention to the structures of the RNA repeats. In this review, we summarize secondary structure probing and crystallographic studies of disease-related RNA repeat sequences. We discuss the unique structural features which can contribute to the pathogenic properties of the repeated runs. In addition, we present the newest reports concerning structural data linked to therapeutic approaches.For further resources related to this article, please visit the WIREs website.Crystallographic structures of RNA repeats associated with neurological disorders.
      PubDate: 2017-01-28T02:10:44.596532-05:
      DOI: 10.1002/wrna.1412
       
  • mRNA localization as a rheostat to regulate subcellular gene expression
    • Authors: Nevraj S. Kejiou; Alexander F. Palazzo
      Abstract: It is currently believed that certain messenger RNAs (mRNAs) are localized to distinct subcellular regions to efficiently target their encoded proteins. However, this simplistic model does not explain why in certain scenarios mRNA localization is dispensable for proper protein distribution. In other cases, mRNA localization is accompanied by translational silencing and degradation by the localization machinery. Here we propose that in certain scenarios mRNAs are localized so that they can either be stabilized and translated, or silenced and degraded, in response to the needs of the subcellular locale. In these cases, the localized mRNA, and its cadre of associated factors, act as a rheostat that regulates protein production and/or mRNA stability in response to the needs of its immediate subcellular environment.For further resources related to this article, please visit the WIREs website.Each localized mRNAs receives input from its subcellular locale and responds as a rheostat to output new proteins to meet local demands.
      PubDate: 2017-01-24T21:45:32.277306-05:
      DOI: 10.1002/wrna.1416
       
  • Regulation of mRNA following brain ischemia and reperfusion
    • Authors: Donald J. DeGracia
      Abstract: There is growing appreciation that mRNA regulation plays important roles in disease and injury. mRNA regulation and ribonomics occur in brain ischemia and reperfusion (I/R) following stroke and cardiac arrest and resuscitation. It was recognized over 40 years ago that translation arrest (TA) accompanies brain I/R and is now recognized as part of the intrinsic stress responses triggered in neurons. However, neuron death correlates to a prolonged TA in cells fated to undergo delayed neuronal death (DND). Dysfunction of mRNA regulatory processes in cells fated to DND prevents them from translating stress-induced mRNAs such as heat shock proteins. The morphological and biochemical studies of mRNA regulation in postischemic neurons are discussed in the context of the large variety of molecular damage induced by ischemic injury. Open issues and areas of future investigation are highlighted. A sober look at the molecular complexity of ischemia-induced neuronal injury suggests that a network framework will assist in making sense of this complexity. The ribonomic network sits between the gene network and the various protein and metabolic networks. Thus, targeting the ribonomic network may prove more effective at neuroprotection than targeting specific molecular pathways, for which all efforts have failed to the present time to stop DND in stroke and after cardiac arrest.For further resources related to this article, please visit the WIREs website.Dramatic image of CA3 neuron after 10-min brain ischemia and 1-h reperfusion shows redistribution of HuR (red) and polyadenylated mRNAs (green).
      PubDate: 2017-01-17T23:55:50.354326-05:
      DOI: 10.1002/wrna.1415
       
  • Bioinformatic tools for analysis of CLIP ribonucleoprotein data
    • Authors: Supriyo De; Myriam Gorospe
      Abstract: Investigating the interactions of RNA-binding proteins (RBPs) with RNAs is a complex task for molecular and computational biologists. The molecular biology techniques and the computational approaches to understand RBP–RNA (or ribonucleoprotein, RNP) interactions have advanced considerably over the past few years and numerous and diverse software tools have been developed to analyze these data. Accordingly, laboratories interested in RNP biology face the challenge of choosing adequately among the available software tools those that best address the biological problem they are studying. Here, we focus on state-of-the-art molecular biology techniques that employ crosslinking and immunoprecipitation (CLIP) of an RBP to study and map RNP interactions. We review the different software tools and databases available to analyze the most widely used CLIP methods, HITS-CLIP, PAR-CLIP, and iCLIP.Overview of CLIP-Seq analysis, from the isolation of cellular RNPs to the identification and analysis of RBP-bound RNA segments using the bioinformatic tools described in this review.
      PubDate: 2016-12-23T00:31:16.732754-05:
      DOI: 10.1002/wrna.1404
       
  • Regulation of mRNA turnover in cystic fibrosis lung disease
    • Authors: Roopa Biswas; Parameet Kumar, Harvey B. Pollard
      Abstract: Cystic fibrosis (CF) is an autosomal recessive disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del-CFTR being the most frequent mutation. The CF lung is characterized by a hyperinflammatory phenotype and is regulated by multiple factors that coordinate its pathophysiology. In CF the expression of CFTR as well as proinflammatory genes are regulated at the level of messenger RNA (mRNA) stability, which subsequently affect translation. These mechanisms are mediated by inflammatory RNA-binding proteins as well as small endogenous noncoding microRNAs, in coordination with cellular signaling pathways. These regulatory factors exhibit altered expression and function in vivo in the CF lung, and play a key role in the pathophysiology of CF lung disease. In this review, we have described the role of mRNA stability and associated regulatory mechanisms in CF lung disease.For further resources related to this article, please visit the WIREs website.Various trans-factors (RNA-binding proteins and/or miRNAs) interact with cis-elements on the mRNA 3′-UTR sequences and regulate the expression of F508del-CFTR and proinflammatory chemokine and cytokine genes (like IL-8 and IL-6) in the cystic fibrosis airway. The concerted effect of these factors and the resulting complex regulatory network regulate the CF disease phenotype.
      PubDate: 2016-11-13T20:55:23.36762-05:0
      DOI: 10.1002/wrna.1408
       
  • RNA-mediated signal perception in pathogenic bacteria
    • Abstract: Bacterial pathogens encounter several different environments during an infection, many of them possibly being detrimental. In order to sense its surroundings and adjust the gene expression accordingly, different regulatory schemes are undertaken. With these, the bacterium appropriately can differentiate between various environmental cues to express the correct virulence factor at the appropriate time and place. An attractive regulator device is RNA, which has an outstanding ability to alter its structure in response to external stimuli, such as metabolite concentration or alterations in temperature, to control its downstream gene expression. This review will describe the function of riboswitches and thermometers, with a particular emphasis on regulatory RNAs being important for bacterial pathogenicity.For further resources related to this article, please visit the WIREs website.RNA sensing in pathogenic bacteria.
       
  • Emerging roles of hnRNPA1 in modulating malignant transformation
    • Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes such as processing of heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs, RNA splicing, transactivation of gene expression, and modulation of protein translation. hnRNPA1 is the most abundant and ubiquitously expressed member of this protein family and has been shown to be involved in multiple molecular events driving malignant transformation. In addition to selective mRNA splicing events promoting expression of specific protein variants, hnRNPA1 regulates the gene expression and translation of several key players associated with tumorigenesis and cancer progression. Here, we will summarize our current knowledge of the involvement of hnRNPA1 in cancer, including its roles in regulating cell proliferation, invasiveness, metabolism, adaptation to stress and immortalization.For further resources related to this article, please visit the WIREs website.hnRNPA1 is involved in multiple biological processes within the cell nucleus and cytoplasm. Counter-clockwise: hnRNPA1 regulates mRNA stability, the transcription of G-quadruplex containing genes, the nuclear export and translational de-repression of IRES-containing mRNAs, mRNA splicing and telomere length maintenance.
       
  • The La and related RNA-binding proteins (LARPs): structures, functions,
           and evolving perspectives
    • Abstract: La was first identified as a polypeptide component of ribonucleic protein complexes targeted by antibodies in autoimmune patients and is now known to be a eukaryote cell-ubiquitous protein. Structure and function studies have shown that La binds to a common terminal motif, UUU-3′-OH, of nascent RNA polymerase III (RNAP III) transcripts and protects them from exonucleolytic decay. For precursor-tRNAs, the most diverse and abundant of these transcripts, La also functions as an RNA chaperone that helps to prevent their misfolding. Related to this, we review evidence that suggests that La and its link to RNAP III were significant in the great expansions of the tRNAomes that occurred in eukaryotes. Four families of La-related proteins (LARPs) emerged during eukaryotic evolution with specialized functions. We provide an overview of the high-resolution structural biology of La and LARPs. LARP7 family members most closely resemble La but function with a single RNAP III nuclear transcript, 7SK, or telomerase RNA. A cytoplasmic isoform of La protein as well as LARPs 6, 4, and 1 function in mRNA metabolism and translation in distinct but similar ways, sometimes with the poly(A)-binding protein, and in some cases by direct binding to poly(A)-RNA. New structures of LARP domains, some complexed with RNA, provide novel insights into the functional versatility of these proteins. We also consider LARPs in relation to ancestral La protein and potential retention of links to specific RNA-related pathways. One such link may be tRNA surveillance and codon usage by LARP-associated mRNAs.For further resources related to this article, please visit the WIREs website.La and La-related proteins (LARPs) share a La module RNA-binding platform and serve a variety of fundamental functions. La and its homologs LARP7, p65, and p43 associate with RNA polymerase-III-derived small RNAs in the nucleus, whereas LARPs 1, 4, and 6 function with cytoplasmic mRNAs.
       
  • Ancient and modern: hints of a core post-transcriptional network driving
           chemotherapy resistance in ovarian cancer
    • Abstract: RNA-binding proteins (RBPs) and noncoding (nc)RNAs (such as microRNAs, long ncRNAs, and others) cooperate within a post-transcriptional network to regulate the expression of genes required for many aspects of cancer behavior including its sensitivity to chemotherapy. Here, using an RBP-centric approach, we explore the current knowledge surrounding contributers to post-transcriptional gene regulation (PTGR) in ovarian cancer and identify commonalities that hint at the existence of an evolutionarily conserved core PTGR network. This network regulates survival and chemotherapy resistance in the contemporary context of the cancer cell. There is emerging evidence that cancers become dependent on PTGR factors for their survival. Further understanding of this network may identify innovative therapeutic targets as well as yield crucial insights into the hard-wiring of many malignancies, including ovarian cancer.For further resources related to this article, please visit the WIREs website.(a)–(c) RNA-binding proteins influence epithelial ovarian cancer (EOC) progression through complex networks with mRNAs, noncoding RNAs, and other proteins. (a) RNA-binding motif protein 3 (RBM3) regulates platinum sensitivity and patient survival through regulation of mRNAs involved in apoptosis and the stress response. (b) HuR exerts an oncogenic effect through stabilization and therefore increased translation of a range of mRNAs. (c) RNA-binding proteins, such as YB1, LARP1, and IMP1 may converge on multiple subsets of mRNAs and signaling pathways as part of a network that drives progression of EOC and/or resistance to chemotherapy.
       
  • Single cell transcriptomics of noncoding RNAs and their cell-specificity
    • Abstract: Recent developments of single cell transcriptome profiling methods have led to the realization that many seemingly homogeneous cells have surprising levels of expression variability. The biological implications of the high degree of variability is unclear but one possibility is that many genes are restricted in expression to small lineages of cells, suggesting the existence of many more cell types than previously estimated. Noncoding RNA (ncRNA) are thought to be key parts of gene regulatory processes and their single cell expression patterns may help to dissect the biological function of single cell variability. Technology for measuring ncRNA in single cell is still in development and most of the current single cell datasets have reliable measurements for only long noncoding RNA (lncRNA). Most works report that lncRNAs show lineage-specific restricted expression patterns, which suggest that they might determine, at least in part, lineage fates and cell subtypes. However, evidence is still inconclusive as to whether lncRNAs and other ncRNAs are more lineage-specific than protein-coding genes. Nevertheless, measurement of ncRNAs in single cells will be important for studies of cell types and single cell function.For further resources related to this article, please visit the WIREs website.Single cell transcriptome analysis reveals cell-to-cell variability in noncoding RNA expression
       
  • An emerging model organism Caenorhabditis elegans for alternative pre-mRNA
           processing in vivo
    • Abstract: A nematode Caenorhabditis elegans is an intron-rich organism and up to 25% of its pre-mRNAs are estimated to be alternatively processed. Its compact genomic organization enables construction of fluorescence splicing reporters with intact genomic sequences and visualization of alternative processing patterns of interest in the transparent living animals with single-cell resolution. Genetic analysis with the reporter worms facilitated identification of trans-acting factors and cis-acting elements, which are highly conserved in mammals. Analysis of unspliced and partially spliced pre-mRNAs in vivo raised models for alternative splicing regulation relying on specific order of intron excision. RNA-seq analysis of splicing factor mutants and CLIP-seq analysis of the factors allow global search for target genes in the whole animal. An mRNA surveillance system is not essential for its viability or fertility, allowing analysis of unproductively spliced noncoding mRNAs. These features offer C. elegans as an ideal model organism for elucidating alternative pre-mRNA processing mechanisms in vivo. Examples of isoform-specific functions of alternatively processed genes are summarized.For further resources related to this article, please visit the WIREs website.Recent progress in fluorescence reporter system and deep sequencing technologies turn C. elegans an excellent multicellular model organism for elucidating pre-mRNA processing regulation in vivo
       
  • RNA structure, binding, and coordination in Arabidopsis
    • Abstract: From the moment of transcription, up through degradation, each RNA transcript is bound by an ever-changing cohort of RNA binding proteins. The binding of these proteins is regulated by both the primary RNA sequence, as well as the intramolecular RNA folding, or secondary structure, of the transcript. Thus, RNA secondary structure regulates many post-transcriptional processes. With the advent of next generation sequencing, several techniques have been developed to generate global landscapes of both RNA–protein interactions and RNA secondary structure. In this review, we describe the current state of the field detailing techniques to globally interrogate RNA secondary structure and/or RNA–protein interaction sites, as well as our current understanding of these features in the transcriptome of the model plant Arabidopsis thaliana.For further resources related to this article, please visit the WIREs website.An overview of techniques used to interrogate in vitro, in vivo, and genome-wide techniques used to study RNA-protein interactions.(A-B) In vitro techniques. (A) Electrophoretic mobility shift assays (EMSAs). (B) Systematic evolution of ligands by exponential enrichment (SELEX). (C-E) Target-specific in vivo techniques. (C) RNA immunoprecipitation (RIP). RIP can be followed by RT-qPCR (RIP-qPCR), microarray (RIP-chip), or RNA sequencing (RIP-seq). (D) Crosslinking followed by Immunoprecipitation (CLIP). CLIP can be followed by RT-qPCR (CLIP-qPCR), microarray (CLIP-chip), or RNA sequencing (CLIP-seq). (E) Photoactivatable ribonucleoside enhanced crosslinking and immunoprecipitation (PAR-CLIP). (F-G) Genome-wide techniques. (F) Global photoactivatable ribonucleoside enhanced crosslinking and immunoprecipitation (gPAR-CLIP). (G) Protein interaction profile sequencing (PIP-seq).
       
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  • Discovery and function of transfer RNA-derived fragments and their role in
           disease
    • Abstract: Until recently, transfer RNAs (tRNAs) were thought to function in protein translation only. However, recent findings demonstrate that both pre- and mature tRNAs can undergo endonucleolytic cleavage by different ribonucleases originating different types of small non-coding RNAs, known as tRNA-derived fragments (tRFs). tRFs are classified according to their origin and are implicated in various cellular processes, namely apoptosis, protein synthesis control, and RNA interference. Although their functions are still poorly understood, their mechanisms of action vary according to the tRF sub-type. Several tRFs have been associated with cancer, neurodegenerative disorders, and viral infections and growing evidence shows that they may constitute novel molecular targets for modulating pathological processes. Here, we recapitulate the current knowledge of tRF biology, highlight the known functions and mechanisms of action of the different sub-classes of tRFs and discuss their implications in human disease.For further resources related to this article, please visit the WIREs website.tRFs derive from tRNAs and constitute a novel and heterogeneous class of small non-coding RNAs involved in normal cell biology and in cancer, neurodegenerative disorders, and viral infections.
       
  • Chimeric RNAs in cancer and normal physiology
    • Abstract: Traditionally, chimeric RNAs were considered to be exclusive to cancer cells. When occasionally observed in normal samples, they were usually considered to be transcriptional ‘noises,’ or artifacts due to template switching during the reverse transcription and/or Polymerase chain reaction (PCR) steps of experimentation. However, with the advances being made in next generation sequencing technologies and software tools, as well as the accumulation of new experimental evidences, increasing numbers of chimeric transcripts are being identified in noncancerous tissues and cells. Recent studies have also demonstrated functional relevance, for at least a subset of chimeric RNAs in normal physiology. The advances have resulted in an influx of knowledge; this knowledge indicates that chimeric RNAs are a component of basic biology, and thus challenging traditional dogma. In addition to chromosomal rearrangement, chimeric RNAs can also be formed via different molecular mechanisms including cis-splicing of adjacent genes (cis-SAGe) and trans-splicing, as well as others. Little is known about the details of these noncanonical splicing processes. However, research in this new field promises to not only advance our basic understanding of the human genome and gene regulation, but also lead to improvements in clinical practice, especially in the areas of cancer diagnostics and treatment.For further resources related to this article, please visit the WIREs website.Chimeric RNAs can be generated not only by chromosomal rearrangements at DNA level, but also by intergenic splicing at RNA level. Nowadays, they are often identified through RNA-Seq. Chimeric RNAs are demonstrated not only to be the elusive features of cancer cells but also present in normal physiology. They can have diverse functions. This review summarized the generating mechanisms of chimeric RNAs, discussed different models, described approaches to identify chimeric RNAs, highlighted their relevance in cancer and normal cells, and offered our insights on the topic and directions for the future research.
       
  • mRNA decay: an adaptation tool for the environmental fungal pathogen
           Cryptococcus neoformans
    • Abstract: Fungi are ubiquitous in the environment and humans constantly encounter them in the soil, air, water, and food. The vast majority of these interactions are inconsequential. However, in the context of immunodeficiency precipitated by HIV infection, hematologic malignancy, or transplantation, a small subset of fungi can cause devastating, systemic infection. The most deadly of the opportunistic environmental fungi, Cryptococcus neoformans, is estimated to cause hundreds of thousands of deaths per year, mostly in the context of HIV co-infection. The cellular processes that mediate adaptation to the host environment are of great interest as potential novel therapeutic targets. One such cellular process important for host adaptation is mRNA decay, which mediates the specific degradation of subsets of functionally related mRNAs in response to stressors relevant to pathogenesis, including human core body temperature, carbon limitation, and reactive oxygen stress. Thus, for C. neoformans, host adaptation requires mRNA decay to mediate rapid transcriptome remodeling in the face of stressors encountered in the host. Several nodes of stress-responsive signaling that govern the stress-responsive transcriptome also control the decay rate of mRNAs cleared from the ribosome during stress, suggesting an additional layer of coupling between mRNA synthesis and decay that allows C. neoformans to be a successful pathogen of humans.For further resources related to this article, please visit the WIREs website.mRNA decay provides agility to the Cryptococcus neoformans transcriptome during both the response to and recovery from stress.13
       
 
 
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