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  • Transcription and splicing: A two-way street.
    WIREs RNA (IF 6.913) Pub Date : 2020-03-03
    Michael Tellier,Isabella Maudlin,Shona Murphy

    RNA synthesis by RNA polymerase II and RNA processing are closely coupled during the transcription cycle of protein-coding genes. This coupling affords opportunities for quality control and regulation of gene expression and the effects can go in both directions. For example, polymerase speed can affect splice site selection and splicing can increase transcription and affect the chromatin landscape

  • Localization elements and zip codes in the intracellular transport and localization of messenger RNAs in Saccharomyces cerevisiae.
    WIREs RNA (IF 6.913) Pub Date : 2020-02-26
    Anusha Chaudhuri,Subhadeep Das,Biswadip Das

    Intracellular trafficking and localization of mRNAs provide a mechanism of regulation of expression of genes with excellent spatial control. mRNA localization followed by localized translation appears to be a mechanism of targeted protein sorting to a specific cell-compartment, which is linked to the establishment of cell polarity, cell asymmetry, embryonic axis determination, and neuronal plasticity

  • Conservation of a core neurite transcriptome across neuronal types and species.
    WIREs RNA (IF 6.913) Pub Date : 2020-02-14
    Nicolai von Kügelgen,Marina Chekulaeva

    The intracellular localization of mRNAs allows neurons to control gene expression in neurite extensions (axons and dendrites) and respond rapidly to local stimuli. This plays an important role in diverse processes including neuronal growth and synaptic plasticity, which in turn serves as a foundation for learning and memory. Recent high-throughput analyses have revealed that neurites contain hundreds

  • Retroelement origins of pre-mRNA splicing.
    WIREs RNA (IF 6.913) Pub Date : 2020-02-11
    Daniel B Haack,Navtej Toor

    Recent cryo-EM structures of a group II intron caught in the process of invading DNA have given new insight into the mechanisms of both splicing and retrotransposition. Conformational dynamics involving the branch-site helix domain VI are responsible for substrate exchange between the two steps of splicing. These structural rearrangements have strong parallels with the movement of the branch-site helix

  • TRIM25 and its emerging RNA-binding roles in antiviral defense.
    WIREs RNA (IF 6.913) Pub Date : 2020-01-28
    Nila Roy Choudhury,Gregory Heikel,Gracjan Michlewski

    The innate immune system is the body's first line of defense against viruses, with pattern recognition receptors (PRRs) recognizing molecules unique to viruses and triggering the expression of interferons and other anti-viral cytokines, leading to the formation of an anti-viral state. The tripartite motif containing 25 (TRIM25) is an E3 ubiquitin ligase thought to be a key component in the activation

  • Following the messenger: Recent innovations in live cell single molecule fluorescence imaging.
    WIREs RNA (IF 6.913) Pub Date : 2020-01-28
    Andreas Schmidt,Guoming Gao,Saffron R Little,Ameya P Jalihal,Nils G Walter

    Messenger RNAs (mRNAs) convey genetic information from the DNA genome to proteins and thus lie at the heart of gene expression and regulation of all cellular activities. Live cell single molecule tracking tools enable the investigation of mRNA trafficking, translation and degradation within the complex environment of the cell and in real time. Over the last 5 years, nearly all tools within the mRNA

  • Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).
    WIREs RNA (IF 6.913) Pub Date : 2020-01-23
    Christopher W Schultz,Ranjan Preet,Teena Dhir,Dan A Dixon,Jonathan R Brody

    Altered gene expression is a characteristic feature of many disease states such as tumorigenesis, and in most cancers, it facilitates cancer cell survival and adaptation. Alterations in global gene expression are strongly impacted by post-transcriptional gene regulation. The RNA binding protein (RBP) HuR (ELAVL1) is an established regulator of post-transcriptional gene regulation and is overexpressed

  • A molecular-level perspective on the frequency, distribution, and consequences of messenger RNA modifications.
    WIREs RNA (IF 6.913) Pub Date : 2020-01-21
    Joshua D Jones,Jeremy Monroe,Kristin S Koutmou

    Cells use chemical modifications to alter the sterics, charge, and conformations of large biomolecules, modulating their biogenesis, function, and stability. Until recently post-transcriptional RNA modifications were thought to be largely limited to nonprotein coding RNA species. However, this dogma has rapidly transformed with the discovery of a host of modifications in protein coding messenger RNAs

  • Noncoding RNAs: New regulatory code in chondrocyte apoptosis and autophagy.
    WIREs RNA (IF 6.913) Pub Date : 2020-01-10
    Siyu Jiang,Yi Liu,Bilian Xu,Yan Zhang,Min Yang

    Osteoarthritis (OA) is a bone and joint disease characterized by progressive cartilage degradation. In the face of global trends of population aging, OA is expected to become the fourth most common disabling disease by 2020. Nevertheless, the detailed pathogenesis of OA has not yet been elucidated. Noncoding RNAs (ncRNAs), including long noncoding RNAs, microRNAs, and circular RNAs, do not encode proteins

  • Alternative splicing programming of axon formation.
    WIREs RNA (IF 6.913) Pub Date : 2020-01-10
    Sika Zheng

    Alternative pre-mRNA splicing generates multiple mRNA isoforms of different structures and functions from a single gene. While the prevalence of alternative splicing control is widely recognized, and the underlying regulatory mechanisms have long been studied, the physiological relevance and biological necessity for alternative splicing are only slowly being revealed. Significant inroads have been

  • On the role of mRNA secondary structure in bacterial translation.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-24
    Claude Chiaruttini,Maude Guillier

    Messenger RNA (mRNA) is no longer considered as a mere informational molecule whose sole function is to convey the genetic information specified by DNA to the ribosome. Beyond this primary function, mRNA also contains additional instructions that influence the way and the extent to which this message is translated by the ribosome into protein(s). Indeed, owing to its intrinsic propensity to quickly

  • Computational methods for ribosome profiling data analysis.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-24
    Stephen J Kiniry,Audrey M Michel,Pavel V Baranov

    Since the introduction of the ribosome profiling technique in 2009 its popularity has greatly increased. It is widely used for the comprehensive assessment of gene expression and for studying the mechanisms of regulation at the translational level. As the number of ribosome profiling datasets being produced continues to grow, so too does the need for reliable software that can provide answers to the

  • The cell stress response: extreme times call for post-transcriptional measures.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-21
    Mariavittoria Pizzinga,Robert F Harvey,Gavin D Garland,Ryan Mordue,Veronica Dezi,Manasa Ramakrishna,Aristeidis Sfakianos,Mie Monti,Thomas E Mulroney,Tuija Poyry,Anne E Willis

    Following cell stress, a wide range of molecular pathways are initiated to orchestrate the stress response and enable adaptation to an environmental or intracellular perturbation. The post-transcriptional regulation strategies adopted during the stress response result in a substantial reorganization of gene expression, designed to prepare the cell for either acclimatization or programmed death, depending

  • Nuclear sorting of RNA.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-11
    William Garland,Torben Heick Jensen

    The majority of the mammalian genome is transcribed by RNA polymerase II, yielding a vast amount of noncoding RNA (ncRNA) in addition to the standard production of mRNA. The typical nuclear biogenesis of mRNA relies on the tightly controlled coupling of co- and post-transcriptional processing events, which ultimately results in the export of transcripts into the cytoplasm. These processes are subject

  • mRNA 3' end formation in plants: Novel connections to growth, development and environmental responses.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-07
    Arthur G Hunt

    3' end processing and mRNA polyadenylation is a vital aspect of gene expression in eukaryotes, and also a step at which expression may be regulated. A spate of recent research in plants links different subunits of the polyadenylation complex with growth and development. These reports provide insight into mechanisms by which APA may be regulated, and perhaps into mechanisms by which pre-mRNAs are processed

  • Epitranscriptomic marks: Emerging modulators of RNA virus gene expression.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-06
    Rachel Netzband,Cara T Pager

    Epitranscriptomics, the study of posttranscriptional chemical moieties placed on RNA, has blossomed in recent years. This is due in part to the emergence of high-throughput detection methods as well as the burst of discoveries showing biological function of select chemical marks. RNA modifications have been shown to affect RNA structure, localization, and functions such as alternative splicing, stabilizing

  • The potential of engineered eukaryotic RNA-binding proteins as molecular tools and therapeutics.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-03
    Carl R Shotwell,John D Cleary,J Andrew Berglund

    Eukaroytic RNA-binding proteins (RBPs) recognize and process RNAs through recognition of their sequence motifs via RNA-binding domains (RBDs). RBPs usually consist of one or more RBDs and can include additional functional domains that modify or cleave RNA. Engineered RBPs have been used to answer basic biology questions, control gene expression, locate viral RNA in vivo, as well as many other tasks

  • What is the switch for coupling transcription and splicing? RNA Polymerase II C-terminal domain phosphorylation, phase separation and beyond.
    WIREs RNA (IF 6.913) Pub Date : 2019-11-03
    Hiroshi Maita,Shinichi Nakagawa

    Phosphorylation of the RNA polymerase II C-terminal domain (Pol II CTD) has important roles in the kinetic coupling of splicing with transcription, which is essential for many genes to maintain correct splicing patterns. However, because of the extensively repeated low complexity sequences of Pol II CTD, it was unclear how phosphorylation-dependent molecular interactions were able to provide sufficient

  • Connections between 3' end processing and DNA damage response: Ten years later.
    WIREs RNA (IF 6.913) Pub Date : 2019-10-28
    Michael Robert Murphy,Frida Esther Kleiman

    Ten years ago we reviewed how the cellular DNA damage response (DDR) is controlled by changes in the functional and structural properties of nuclear proteins, resulting in a timely coordinated control of gene expression that allows DNA repair. Expression of genes that play a role in DDR is regulated not only at transcriptional level during mRNA biosynthesis but also by changing steady-state levels

  • Current overview on viroid-host interactions.
    WIREs RNA (IF 6.913) Pub Date : 2019-10-22
    Charith Raj Adkar-Purushothama,Jean-Pierre Perreault

    Viroids are one of the most enigmatic highly structured, circular, single-stranded RNA phytopathogens. Although they are not known to code for any peptide, viroids induce visible symptoms in susceptible host plants that resemble those associated with many plant viruses. It is known that viroids induce disease symptoms by direct interaction with host factors; however, the precise mechanism by which

  • The role of RNA G-quadruplexes in human diseases and therapeutic strategies.
    WIREs RNA (IF 6.913) Pub Date : 2019-09-12
    Prakash Kharel,Sumirtha Balaratnam,Nathan Beals,Soumitra Basu

    G-quadruplexes (GQs) are four-stranded secondary structures formed by G-rich nucleic acid sequence(s). DNA GQs are present abundantly in the genome and affect a wide range of processes associated with DNA. Recent studies show that RNA GQs are present in different transcripts, including coding and noncoding areas of mRNA, telomeric RNA as well as in other premature and mature noncoding RNAs. When present

  • Methods for analysis of circular RNAs.
    WIREs RNA (IF 6.913) Pub Date : 2019-09-05
    Poonam R Pandey,Rachel Munk,Gautam Kundu,Supriyo De,Kotb Abdelmohsen,Myriam Gorospe

    Eukaryotic cells express a myriad of circular RNAs (circRNAs), many of them displaying tissue-specific expression patterns. They arise from linear precursor RNAs in which 5' and 3' ends become covalently ligated. Given these features, biochemical and computational approaches traditionally used to study linear RNA must be adapted for analysis of circular RNAs. Such circRNA-specific methodologies are

  • Highlighting transcribed ultraconserved regions in human diseases.
    WIREs RNA (IF 6.913) Pub Date : 2019-09-05
    Erika Pereira Zambalde,Carolina Mathias,Ana Carolina Rodrigues,Enilze M de Souza Fonseca Ribeiro,Daniela Fiori Gradia,George A Calin,Jaqueline Carvalho de Oliveira

    Ultraconserved regions (UCRs) are 481 DNA segments longer than 200 bp in length that are completely conserved among human, mouse, and rat and, extremely conserved across disparate taxa. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, but most of them remain uncharacterized. In addition, it was demonstrated that T-UCRs have a tissue-specific expression, and a differential expression

  • Cluster miRNAs and cancer: Diagnostic, prognostic and therapeutic opportunities.
    WIREs RNA (IF 6.913) Pub Date : 2019-08-22
    Shama Prasada Kabekkodu,Vaibhav Shukla,Vinay Koshy Varghese,Divya Adiga,Padacherri Vethil Jishnu,Sanjiban Chakrabarty,Kapaettu Satyamoorthy

    MiRNAs are class of noncoding RNA important for gene expression regulation in many plants, animals and viruses. MiRNA clusters contain a set of two or more miRNA encoding genes, transcribed together as polycistronic miRNAs. Currently, there are approximately 159 miRNA clusters reported in the human genome consisting of miRNAs ranging from two or more miRNA genes. A large proportion of clustered miRNAs

  • Approaches for measuring the dynamics of RNA-protein interactions.
    WIREs RNA (IF 6.913) Pub Date : 2019-08-20
    Donny D Licatalosi,Xuan Ye,Eckhard Jankowsky

    RNA-protein interactions are pivotal for the regulation of gene expression from bacteria to human. RNA-protein interactions are dynamic; they change over biologically relevant timescales. Understanding the regulation of gene expression at the RNA level therefore requires knowledge of the dynamics of RNA-protein interactions. Here, we discuss the main experimental approaches to measure dynamic aspects

  • RNA mimicry in post-transcriptional regulation by aminoacyl tRNA synthetases.
    WIREs RNA (IF 6.913) Pub Date : 2019-08-15
    Ofri Levi,Shahar Garin,Yoav Arava

    Aminoacyl tRNA synthetases (aaRS) are well studied for their roles in tRNA charging with cognate amino acid. Nevertheless, numerous lines of evidence indicate that these proteins have roles other than tRNA charging. These include coordination of cellular signaling cascades, induction of cytokines outside the cell and transcription regulation. Herein, we focus on their roles in post-transcriptional

  • Fusion transcripts: Unexploited vulnerabilities in cancer?
    WIREs RNA (IF 6.913) Pub Date : 2019-08-13
    Carla Neckles,Soumya Sundara Rajan,Natasha J Caplen

    Gene fusions are an important class of mutations in several cancer types and include genomic rearrangements that fuse regulatory or coding elements from two different genes. Analysis of the genetics of cancers harboring fusion oncogenes and the proteins they encode have enhanced cancer diagnosis and in some cases patient treatment. However, the effect of the complex structure of fusion genes on the

  • Chemo-enzymatic treatment of RNA to facilitate analyses.
    WIREs RNA (IF 6.913) Pub Date : 2019-08-08
    Nils Muthmann,Katja Hartstock,Andrea Rentmeister

    Labeling RNA is a recurring problem to make RNA compatible with state-of-the-art methodology and comes in many flavors. Considering only cellular applications, the spectrum still ranges from site-specific labeling of individual transcripts, for example, for live-cell imaging of mRNA trafficking, to metabolic labeling in combination with next generation sequencing to capture dynamic aspects of RNA metabolism

  • How to get away with nonsense: Mechanisms and consequences of escape from nonsense-mediated RNA decay.
    WIREs RNA (IF 6.913) Pub Date : 2019-07-29
    Michael C Dyle,Divya Kolakada,Michael A Cortazar,Sujatha Jagannathan

    Nonsense-mediated RNA decay (NMD) is an evolutionarily conserved RNA quality control process that serves both as a mechanism to eliminate aberrant transcripts carrying premature stop codons, and to regulate expression of some normal transcripts. For a quality control process, NMD exhibits surprising variability in its efficiency across transcripts, cells, tissues, and individuals in both physiological

  • Pat1 RNA-binding proteins: Multitasking shuttling proteins.
    WIREs RNA (IF 6.913) Pub Date : 2019-06-24
    Caroline Vindry,Dominique Weil,Nancy Standart

    Post-transcriptional regulation of gene expression is largely achieved at the level of splicing in the nucleus, and translation and mRNA decay in the cytosol. While the regulation may be global, through the direct inhibition of central factors, such as the spliceosome, translation initiation factors and mRNA decay enzymes, in many instances transcripts bearing specific sequences or particular features

  • Protein kinase R and its cellular regulators in cancer: An active player or a surveillant?
    WIREs RNA (IF 6.913) Pub Date : 2019-06-23
    Yong Sun Lee,Nawapol Kunkeaw,Yeon-Su Lee

    Protein kinase R (PKR), originally known as an antiviral protein, senses various stresses as well as pathogen-driven double-stranded RNAs. Thereby activated PKR provokes diverse downstream events, including eIF2α phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells activation. Consequently, PKR induces apoptosis and inflammation, both of which are highly important in cancer

  • PIWI pathway against viruses in insects.
    WIREs RNA (IF 6.913) Pub Date : 2019-06-10
    Anna Kolliopoulou,Dulce Santos,Clauvis Nji Tizi Taning,Niels Wynant,Jozef Vanden Broeck,Guy Smagghe,Luc Swevers

    Piwi-interacting RNAs (piRNAs) are an animal-specific class of small non-coding RNAs that are generated via a biogenesis pathway distinct from small interfering RNAs (siRNAs) and microRNAs (miRNAs). There are variations in piRNA biogenesis that depend on several factors, such as the cell type (germline or soma), the organism, and the purpose for which they are being produced, such as transposon-targeting

  • mRNA methylation in cell senescence.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-29
    Gabriel Casella,Dimitrios Tsitsipatis,Kotb Abdelmohsen,Myriam Gorospe

    Cellular senescence, a developmental program central to normal aging and aging pathologies, is robustly regulated at the post-transcriptional level. This regulation involves the interaction of RNA-binding proteins and noncoding RNAs with senescence-associated messenger RNAs (mRNAs). There is increasing evidence that these associations are modulated by chemical modifications of specific mRNA nucleotides

  • Nonsense-mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-26
    Aparna Kishor,Sarah E Fritz,J Robert Hogg

    The nonsense-mediated mRNA decay pathway selects and degrades its targets using a dense network of RNA-protein and protein-protein interactions. Together, these interactions allow the pathway to collect copious information about the translating mRNA, including translation termination status, splice junction positions, mRNP composition, and 3'UTR length and structure. The core NMD machinery, centered

  • RNA control in pain: Blame it on the messenger.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-14
    June Bryan I de la Peña,Jane J Song,Zachary T Campbell

    mRNA function is meticulously controlled. We provide an overview of the integral role that posttranscriptional controls play in the perception of painful stimuli by sensory neurons. These specialized cells, termed nociceptors, precisely regulate mRNA polarity, translation, and stability. A growing body of evidence has revealed that targeted disruption of mRNAs and RNA-binding proteins robustly diminishes

  • Recent methodology progress of deep learning for RNA-protein interaction prediction.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-08
    Xiaoyong Pan,Yang Yang,Chun-Qiu Xia,Aashiq H Mirza,Hong-Bin Shen

    Interactions between RNAs and proteins play essential roles in many important biological processes. Benefitting from the advances of next generation sequencing technologies, hundreds of RNA-binding proteins (RBP) and their associated RNAs have been revealed, which enables the large-scale prediction of RNA-protein interactions using machine learning methods. Till now, a wide range of computational tools

  • Alternative polyadenylation and the stress response.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-02
    Jason Sadek,Amr Omer,Derek Hall,Kholoud Ashour,Imed Eddine Gallouzi

    The cellular stress response is a universal mechanism necessary for the survival of all organisms. This multifaceted process is primarily driven by regulation of gene expression to produce an intracellular environment suitable for promoting cell survival and recovery. Posttranscriptional regulatory events are considered as critical mechanisms that modulate core characteristics of mRNA transcripts to

  • The emerging importance of noncoding RNAs in the insecticide tolerance, with special emphasis on Plutella xylostella (Lepidoptera: Plutellidae).
    WIREs RNA (IF 6.913) Pub Date : 2019-05-02
    Luis María Vaschetto,Hernán Mario Beccacece

    Recently generated high-throughput sequencing data sets have shed light on the important regulatory roles of noncoding RNA (ncRNA) molecules in the development of higher organisms. Nowadays it is well-known that regulatory ncRNAs can bind complementary RNA or DNA sequences and recruit chromatin remodelers to selectively modulate gene expression. Consequently, genome sequencing and transcriptomics technologies

  • Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase-separated nuclear paraspeckles.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-01
    Tetsuro Hirose,Tomohiro Yamazaki,Shinichi Nakagawa

    Long noncoding RNAs (lncRNAs) are extremely diverse and have various significant physiological functions. lncRNAs generally associate with specific sets of RNA-binding proteins (RBPs) to form functional ribonucleoprotein (RNP) complexes. NEAT1 is a highly abundant lncRNA in the mammalian cell nucleus that associates with specific RBPs to form NEAT1 RNPs. Intriguingly, cellular NEAT1 RNPs are extraordinarily

  • Classical and emerging techniques to identify and quantify localized RNAs.
    WIREs RNA (IF 6.913) Pub Date : 2019-05-01
    J Matthew Taliaferro

    In essentially every cell, proteins are asymmetrically distributed according to their function. For many genes, this protein sorting problem is solved by transporting RNA molecules encoding the protein, rather than the protein itself, to the desired subcellular location. The protein is then translated on-site to immediately produce a correctly localized protein. This strategy is widely used as thousands

  • Viral modulation of cellular RNA alternative splicing: A new key player in virus-host interactions?
    WIREs RNA (IF 6.913) Pub Date : 2019-04-29
    Simon Boudreault,Patricia Roy,Guy Lemay,Martin Bisaillon

    Upon viral infection, a tug of war is triggered between host cells and viruses to maintain/gain control of vital cellular functions, the result of which will ultimately dictate the fate of the host cell. Among these essential cellular functions, alternative splicing (AS) is an important RNA maturation step that allows exons, or parts of exons, and introns to be retained in mature transcripts, thereby

  • RNA regulatory processes in RNA virus biology.
    WIREs RNA (IF 6.913) Pub Date : 2019-04-29
    Shaun T Cross,Daniel Michalski,Megan R Miller,Jeffrey Wilusz

    Numerous post-transcriptional RNA processes play a major role in regulating the quantity, quality and diversity of gene expression in the cell. These include RNA processing events such as capping, splicing, polyadenylation and modification, but also aspects such as RNA localization, decay, translation, and non-coding RNA-associated regulation. The interface between the transcripts of RNA viruses and

  • Intriguing circles: Conflicts and controversies in circular RNA research.
    WIREs RNA (IF 6.913) Pub Date : 2019-04-29
    Hui-Min Li,Xiu-Lan Ma,Hong-Gang Li

    Circular RNAs (circRNAs) are covalently closed RNA circles without a 5' cap or 3' tail. Since the landmark discovery of ciRS-7/CDR1as functioning as a miR-7 sponge in 2013, circRNAs have become a hot topic in RNA research. CircRNAs have been found to play active roles in cancer, cardiovascular diseases, neurological disorders, and many other diseases. They can function as microRNA (miRNA) sponges,

  • Advances that facilitate the study of large RNA structure and dynamics by nuclear magnetic resonance spectroscopy.
    WIREs RNA (IF 6.913) Pub Date : 2019-04-25
    Huaqun Zhang,Sarah C Keane

    The characterization of functional yet nonprotein coding (nc) RNAs has expanded the role of RNA in the cell from a passive player in the central dogma of molecular biology to an active regulator of gene expression. The misregulation of ncRNA function has been linked with a variety of diseases and disorders ranging from cancers to neurodegeneration. However, a detailed molecular understanding of how

  • MicroRNAs as regulators and effectors of hematopoietic transcription factors.
    WIREs RNA (IF 6.913) Pub Date : 2019-04-21
    MinJung Kim,Curt I Civin,Tami J Kingsbury

    Hematopoiesis is a highly-regulated development process orchestrated by lineage-specific transcription factors that direct the generation of all mature blood cells types, including red blood cells, megakaryocytes, granulocytes, monocytes, and lymphocytes. Under homeostatic conditions, the hematopoietic system of the typical adult generates over 1011 blood cells daily throughout life. In addition, hematopoiesis

  • RNA regulation of the antiviral protein 2'-5'-oligoadenylate synthetase.
    WIREs RNA (IF 6.913) Pub Date : 2019-04-15
    Samantha L Schwartz,Graeme L Conn

    The innate immune system is a broad collection of critical intra- and extra-cellular processes that limit the infectivity of diverse pathogens. The 2'-5'-oligoadenylate synthetase (OAS) family of enzymes are important sensors of cytosolic double-stranded RNA (dsRNA) that play a critical role in limiting viral infection by activating the latent ribonuclease (RNase L) to halt viral replication and establish

  • Extracellular RNA in viral-host interactions: Thinking outside the cell.
    WIREs RNA (IF 6.913) Pub Date : 2019-04-08
    Sarah Ressel,Adelina Rosca,Katrina Gordon,Amy H Buck

    Small RNAs and their associated RNA interference (RNAi) pathways underpin diverse mechanisms of gene regulation and genome defense across all three kingdoms of life and are integral to virus-host interactions. In plants, fungi and many animals, an ancestral RNAi pathway exists as a host defense mechanism whereby viral double-stranded RNA is processed to small RNAs that enable recognition and degradation

  • MicroRNAs meet with quantitative trait loci: Small powerful players in regulating quantitative yield traits in rice.
    WIREs RNA (IF 6.913) Pub Date : 2019-03-24
    Ting Peng,Sachin Teotia,Guiliang Tang,Quanzhi Zhao

    MicroRNAs (miRNAs) are small noncoding RNAs which regulate various functions related to growth, development, and stress responses in plants and animals. Rice, Oryza sativa, is one of the most important food crops of the world. In rice, a number of quantitative trait loci (QTL) controlling yield-related traits have been identified. Some of them are actually controlled by miRNAs, which control various

  • miR-146a-5p: Expression, regulation, and functions in cancer.
    WIREs RNA (IF 6.913) Pub Date : 2019-03-20
    Joseph R Iacona,Carol S Lutz

    Cancer as we know it is actually an umbrella term for over 100 very unique malignancies in various tissues throughout the human body. Each type, and even subtype of cancer, has different genetic, epigenetic, and other cellular events responsible for malignant development and metastasis. Recent work has indicated that microRNAs (miRNAs) play a major role in these processes, sometimes by promoting cancer

  • Splicing and neurodegeneration: Insights and mechanisms.
    WIREs RNA (IF 6.913) Pub Date : 2019-03-20
    Sara Nik,Teresa V Bowman

    Splicing is the global cellular process whereby intervening sequences (introns) in precursor messenger RNA (pre-mRNA) are removed and expressed regions (exons) are ligated together, resulting in a mature mRNA transcript that is exported and translated in the cytoplasm. The tightly regulated splicing cycle is also flexible allowing for the inclusion or exclusion of some sequences depending on the specific

  • The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family.
    WIREs RNA (IF 6.913) Pub Date : 2019-03-12
    Wi S Lai,Melissa L Wells,Lalith Perera,Perry J Blackshear

    Tristetraprolin (TTP), the prototype member of the protein family of the same name, was originally discovered as the product of a rapidly inducible gene in mouse cells. Development of a knockout (KO) mouse established that absence of the protein led to a severe inflammatory syndrome, due in part to elevated levels of tumor necrosis factor (TNF). TTP was found to bind directly and with high affinity

  • Writing a wrong: Coupled RNA polymerase II transcription and RNA quality control.
    WIREs RNA (IF 6.913) Pub Date : 2019-03-07
    Sarah A Peck,Katlyn D Hughes,Jose F Victorino,Amber L Mosley

    Processing and maturation of precursor RNA species is coupled to RNA polymerase II transcription. Co-transcriptional RNA processing helps to ensure efficient and proper capping, splicing, and 3' end processing of different RNA species to help ensure quality control of the transcriptome. Many improperly processed transcripts are not exported from the nucleus, are restricted to the site of transcription

  • The cellular landscape of mid-size noncoding RNA.
    WIREs RNA (IF 6.913) Pub Date : 2019-03-06
    Vincent Boivin,Laurence Faucher-Giguère,Michelle Scott,Sherif Abou-Elela

    Noncoding RNA plays an important role in all aspects of the cellular life cycle, from the very basic process of protein synthesis to specialized roles in cell development and differentiation. However, many noncoding RNAs remain uncharacterized and the function of most of them remains unknown. Mid-size noncoding RNAs (mncRNAs), which range in length from 50 to 400 nucleotides, have diverse regulatory

  • Tissue-specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update).
    WIREs RNA (IF 6.913) Pub Date : 2019-02-27
    Clinton C MacDonald

    Alternative polyadenylation (APA) is how genes choose different sites for 3' end formation for mRNAs during transcription. APA often occurs in a tissue- or developmental stage-specific manner that can significantly affect gene activity by changing the protein product generated, the stability of the transcript, its localization within the cell, or its translatability. Despite the important regulatory

  • Stress-induced mRNP granules: Form and function of processing bodies and stress granules.
    WIREs RNA (IF 6.913) Pub Date : 2019-02-21
    Anna R Guzikowski,Yang S Chen,Brian M Zid

    In response to stress, cells must quickly reprogram gene expression to adapt and survive. This is achieved in part by altering levels of mRNAs and their translation into proteins. Recently, the formation of two stress-induced messenger ribonucleoprotein (mRNP) assemblies named stress granules and processing bodies has been postulated to directly impact gene expression during stress. These assemblies

  • Computational approaches for circular RNA analysis.
    WIREs RNA (IF 6.913) Pub Date : 2019-02-20
    Tobias Jakobi,Christoph Dieterich

    Circular RNAs (circRNAs) are a recent addition to the expanding universe of RNA species and originate through back-splicing events from linear primary transcripts. CircRNAs show specific expression profiles with regards to cell type and developmental stage. Importantly, only few circRNAs have been functionally characterized to date. The detection of circRNAs from RNA sequencing data is a complex computational

  • Splicing and cancer: Challenges and opportunities.
    WIREs RNA (IF 6.913) Pub Date : 2019-02-17
    Patricia P Coltri,Maria G P Dos Santos,Guilherme H G da Silva

    Cancer arises from alterations in several metabolic processes affecting proliferation, growth, replication and death of cells. A fundamental challenge in the study of cancer biology is to uncover molecular mechanisms that lead to malignant cellular transformation. Recent genomic analyses revealed that many molecular alterations observed in cancers come from modifications in the splicing process, including

  • Mimicry, deception and competition: The life of competing endogenous RNAs.
    WIREs RNA (IF 6.913) Pub Date : 2019-02-13
    Marc P Grüll,Eric Massé

    Since their discovery, small regulatory RNAs (sRNAs) were thought to be regulated exclusively at the transcriptional level. However, accumulating data from recent reports indicate that posttranscriptional signals can also modulate the function and stability of sRNAs. One of these posttranscriptional signals are competing endogenous RNAs (ceRNAs). Commonly called RNA sponges, ceRNAs can effectively

  • RNAs in the spliceosome: Insight from cryoEM structures.
    WIREs RNA (IF 6.913) Pub Date : 2019-02-06
    Lingdi Zhang,Anne Vielle,Sara Espinosa,Rui Zhao

    Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton RNA-protein complex. The spliceosome undergoes dramatic compositional and conformational changes through the splicing cycle, forming at least 10 distinct complexes. Recent high-resolution cryoEM structures of various spliceosomal complexes revealed unprecedented details of this large molecular machine. This review highlights insight

  • On the edge of degradation: Autophagy regulation by RNA decay.
    WIREs RNA (IF 6.913) Pub Date : 2018-12-17
    Elizabeth Delorme-Axford,Daniel J Klionsky

    Cells must dynamically adapt to altered environmental conditions, particularly during times of stress, to ensure their ability to function effectively and survive. The macroautophagy/autophagy pathway is highly conserved across eukaryotic cells and promotes cell survival during stressful conditions. In general, basal autophagy occurs at a low level to sustain cellular homeostasis and metabolism. However

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