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Wiley Interdisciplinary Reviews. RNA

Helena Covelo-Molares, Marek Bartosovic, Stepanka Vanacova
Eukaryotic RNA can carry more than 100 different types of chemical modifications. Early studies have been focused on modifications of highly abundant RNA, such as ribosomal RNA and transfer RNA, but recent technical advances have made it possible to also study messenger RNA (mRNA). Subsequently, mRNA modifications, namely methylation, have emerged as key players in eukaryotic gene expression regulation. The most abundant and widely studied internal mRNA modification is N6 -methyladenosine (m6 A), but the list of mRNA chemical modifications continues to grow as fast as interest in this field...
June 19, 2018: Wiley Interdisciplinary Reviews. RNA
Rafailia A A Beta, Nikolaos A A Balatsos
Circadian rhythms are ubiquitous time-keeping processes in eukaryotes with a period of ~24 hr. Light is perhaps the main environmental cue (zeitgeber) that affects several aspects of physiology and behaviour, such as sleep/wake cycles, orientation of birds and bees, and leaf movements in plants. Temperature can serve as the main zeitgeber in the absence of light cycles, even though it does not lead to rhythmicity through the same mechanism as light. Additional cues include feeding patterns, humidity, and social rhythms...
June 17, 2018: Wiley Interdisciplinary Reviews. RNA
Sara L Zimmer, Rachel M Simpson, Laurie K Read
Among Euglenozoans, mitochondrial RNA editing occurs in the diplonemids and in the kinetoplastids that include parasitic trypanosomes. Yet U-indel editing, in which open reading frames (ORFs) on mRNAs are generated by insertion and deletion of uridylates in locations dictated by guide RNAs, appears confined to kinetoplastids. The nature of guide RNA and edited mRNA populations has been cursorily explored in a surprisingly extensive number of species over the years, although complete sets of fully edited mRNAs for most kinetoplast genomes are largely missing...
June 11, 2018: Wiley Interdisciplinary Reviews. RNA
Laura L Arthur, Sergej Djuranovic
The abundance of messenger RNA (mRNA) is one of the major determinants of protein synthesis. As such, factors that influence mRNA stability often contribute to gene regulation. Polyadenylation of the 3' end of mRNA transcripts, the poly(A) tail, has long been recognized as one of these regulatory elements given its influence on translation efficiency and mRNA stability. Unwanted translation of the poly(A) tail signals to the cell an aberrant polyadenylation event or the lack of stop codons, which makes this sequence an important element in translation fidelity and mRNA surveillance response...
June 5, 2018: Wiley Interdisciplinary Reviews. RNA
Jongbo Lee, Minjong Kim, Taichi Q Itoh, Chunghun Lim
Ataxin-2 (ATXN2) is a eukaryotic RNA-binding protein that is conserved from yeast to human. Genetic expansion of a poly-glutamine tract in human ATXN2 has been implicated in several neurodegenerative diseases, likely acting through gain-of-function effects. Emerging evidence, however, suggests that ATXN2 plays more direct roles in neural function via specific molecular and cellular pathways. ATXN2 and its associated protein complex control distinct steps in posttranscriptional gene expression, including poly-A tailing, RNA stabilization, microRNA-dependent gene silencing, and translational activation...
June 5, 2018: Wiley Interdisciplinary Reviews. RNA
Bernhard Schaefke, Wei Sun, Yi-Sheng Li, Liang Fang, Wei Chen
"DNA makes RNA makes protein." After transcription, mRNAs undergo a series of intertwining processes to be finally translated into functional proteins. The "posttranscriptional" regulation (PTR) provides cells an extended option to fine-tune their proteomes. To meet the demands of complex organism development and the appropriate response to environmental stimuli, every step in these processes needs to be finely regulated. Moreover, changes in these regulatory processes are important driving forces underlying the evolution of phenotypic differences across different species...
May 31, 2018: Wiley Interdisciplinary Reviews. RNA
Daan C Swarts, Martin Jinek
Cas9 and Cas12a are multidomain CRISPR-associated nucleases that can be programmed with a guide RNA to bind and cleave complementary DNA targets. The guide RNA sequence can be varied, making these effector enzymes versatile tools for genome editing and gene regulation applications. While Cas9 is currently the best-characterized and most widely used nuclease for such purposes, Cas12a (previously named Cpf1) has recently emerged as an alternative for Cas9. Cas9 and Cas12a have distinct evolutionary origins and exhibit different structural architectures, resulting in distinct molecular mechanisms...
May 22, 2018: Wiley Interdisciplinary Reviews. RNA
Debadrita Roy, Purusharth I Rajyaguru
Translation control plays a key role in variety of cellular processes. Translation initiation factors augment translation, whereas translation repressor proteins inhibit translation. Different repressors act by distinct mechanisms to accomplish the repression process. Although messenger RNAs (mRNAs) can be repressed at various steps of translation, most repressors have been reported to target the initiation step. We focus on one such translation repressor, an Arginine-Glycine-Glycine (RGG)-motif containing protein Scd6...
May 22, 2018: Wiley Interdisciplinary Reviews. RNA
Anita Donlic, Amanda E Hargrove
The recognition of RNA functions beyond canonical protein synthesis has challenged the central dogma of molecular biology. Indeed, RNA is now known to directly regulate many important cellular processes, including transcription, splicing, translation, and epigenetic modifications. The misregulation of these processes in disease has led to an appreciation of RNA as a therapeutic target. This potential was first recognized in bacteria and viruses, but discoveries of new RNA classes following the sequencing of the human genome have invigorated exploration of its disease-related functions in mammals...
July 2018: Wiley Interdisciplinary Reviews. RNA
Bruno D Fonseca, Roni M Lahr, Christian K Damgaard, Tommy Alain, Andrea J Berman
The ribosome is an essential unit of all living organisms that commands protein synthesis, ultimately fuelling cell growth (accumulation of cell mass) and cell proliferation (increase in cell number). The eukaryotic ribosome consists of 4 ribosomal RNAs (rRNAs) and 80 ribosomal proteins (RPs). Despite its fundamental role in every living organism, our present understanding of how higher eukaryotes produce the various ribosome components is incomplete. Uncovering the mechanisms utilized by human cells to generate functional ribosomes will likely have far-reaching implications in human disease...
May 2, 2018: Wiley Interdisciplinary Reviews. RNA
Robert A Battaglia, Ailong Ke
After remaining an orphan for over a decade, the ykkC riboswitch family (ykkC, mini-ykkC, and ykkC-III) was recently characterized as guanidine-specific genetic regulatory elements (guanidine-I, II, and III). They respond to increased levels of intracellular guanidine by turning on genes involved in guanidine export and breakdown. Their existence suggests that regulation of intracellular guanidine levels could be an important piece of bacterial physiology which was not appreciated previously. Structural biologists moved exceptionally fast to reveal the guanidine-sensing mechanisms of these riboswitches at the atomic level...
April 26, 2018: Wiley Interdisciplinary Reviews. RNA
Jeremy E Wilusz
The first circular RNA (circRNA) was identified more than 40 years ago, but it was only recently appreciated that circRNAs are common outputs of many eukaryotic protein-coding genes. Some circRNAs accumulate to higher levels than their associated linear mRNAs, especially in the nervous system, and have clear regulatory functions that result in organismal phenotypes. The pre-mRNA splicing machinery generates circRNAs via backsplicing reactions, which are often facilitated by intronic repeat sequences that base pair to one another and bring the intervening splice sites into close proximity...
April 14, 2018: Wiley Interdisciplinary Reviews. RNA
Andrew Santiago-Frangos, Sarah A Woodson
Hfq is a ubiquitous, Sm-like RNA binding protein found in most bacteria and some archaea. Hfq binds small regulatory RNAs (sRNAs), facilitates base pairing between sRNAs and their mRNA targets, and directly binds and regulates translation of certain mRNAs. Because sRNAs regulate many stress response pathways in bacteria, Hfq is essential for adaptation to different environments and growth conditions. The chaperone activities of Hfq arise from multipronged RNA binding by three different surfaces of the Hfq hexamer...
April 6, 2018: Wiley Interdisciplinary Reviews. RNA
Nikolay E Shirokikh, Thomas Preiss
Gene expression universally relies on protein synthesis, where ribosomes recognize and decode the messenger RNA template by cycling through translation initiation, elongation, and termination phases. All aspects of translation have been studied for decades using the tools of biochemistry and molecular biology available at the time. Here, we focus on the mechanism of translation initiation in eukaryotes, which is remarkably more complex than prokaryotic initiation and is the target of multiple types of regulatory intervention...
April 6, 2018: Wiley Interdisciplinary Reviews. RNA
Laura M Urbanski, Nathan Leclair, Olga Anczuków
Defects in alternative splicing are frequently found in human tumors and result either from mutations in splicing-regulatory elements of specific cancer genes or from changes in the regulatory splicing machinery. RNA splicing regulators have emerged as a new class of oncoproteins and tumor suppressors, and contribute to disease progression by modulating RNA isoforms involved in the hallmark cancer pathways. Thus, dysregulation of alternative RNA splicing is fundamental to cancer and provides a potentially rich source of novel therapeutic targets...
July 2018: Wiley Interdisciplinary Reviews. RNA
Ji Heon Noh, Kyoung Mi Kim, Waverly G McClusky, Kotb Abdelmohsen, Myriam Gorospe
Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides found throughout the cell that lack protein-coding function. Their functions are closely linked to their interaction with RNA-binding proteins (RBPs) and nucleic acids. Nuclear lncRNAs have been studied extensively, revealing complexes with structural and regulatory roles that enable gene organization and control transcription. Cytoplasmic lncRNAs are less well understood, but accumulating evidence indicates that they also form complexes with diverse structural and regulatory functions...
May 2018: Wiley Interdisciplinary Reviews. RNA
David Rekosh, Marie-Louise Hammarskjold
Intron retention (IR), where one or more introns remain in the RNA after splicing, was long thought to be rare in mammalian cells, albeit common in plants and some viruses. Largely due to the development of better methods for RNA analysis, it has now been recognized that IR is much more common than previously thought and that this mechanism is likely to play an important role in mammalian gene regulation. To date, most publications and reviews about IR have described the resulting mRNAs as "dead end" products, with no direct consequence for the proteome...
May 2018: Wiley Interdisciplinary Reviews. RNA
Jonathan R Brody, Dan A Dixon
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal patient outcomes. The underlying core genetic drivers of disease have been identified in human tumor specimens and described in genetically engineered mouse models. These genetic drivers of PDAC include KRAS signaling, TP53 mutations, and genetic loss of the SMAD4 tumor suppressor protein. Beyond the known mutational landscape of PDAC genomes, alternative disrupted targets that extend beyond conventional genetic mutations have been elusive and understudied in the context of PDAC cell therapeutic resistance and survival...
May 2018: Wiley Interdisciplinary Reviews. RNA
Manon Torres, Denis Becquet, Jean-Louis Franc, Anne-Marie François-Bellan
The circadian clock drives daily rhythms of multiple physiological processes, allowing organisms to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of at least 30% of expressed genes. While the ability for the endogenous timekeeping system to generate a 24-hr cycle is a cell-autonomous mechanism based on negative autoregulatory feedback loops of transcription and translation involving core-clock genes and their protein products, it is now increasingly evident that additional mechanisms also govern the circadian oscillations of clock-controlled genes...
May 2018: Wiley Interdisciplinary Reviews. RNA
Yongfeng Jin, Haiyang Dong, Yang Shi, Lina Bian
Pre-mRNA alternative splicing is an important mechanism used to expand protein diversity in higher eukaryotes, and mutually exclusive splicing is a specific type of alternative splicing in which only one of the exons in a cluster is included in functional transcripts. The most extraordinary example of this is the Drosophila melanogaster Down's syndrome cell adhesion molecule gene (Dscam), which potentially encodes 38,016 different isoforms through mutually exclusive splicing. Mutually exclusive splicing is a unique and challenging model that can be used to elucidate the evolution, regulatory mechanism, and function of alternative splicing...
May 2018: Wiley Interdisciplinary Reviews. RNA
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