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Wiley Interdisciplinary Reviews. RNA

Sherif Abou Elela, Xinhua Ji
The double-stranded RNA-binding protein (dsRBP) family controls RNA editing, stability, and function in all eukaryotes. The central feature of this family is the recognition of a generic RNA duplex using highly conserved double-stranded RNA-binding domain (dsRBD) that recognizes the characteristic distance between the minor grooves created by the RNA helix. Variations on this theme that confer species and functional specificities have been reported but most dsRBPs retain their capacity to bind generic dsRNA...
December 11, 2018: Wiley Interdisciplinary Reviews. RNA
Zheng Xing, Wai Kit Ma, Elizabeth J Tran
The mammalian DEAD-box RNA helicase DDX5, its paralog DDX17, and their orthologs in Saccharomyces cerevisiae and Drosophila melanogaster, namely Dbp2 and Rm62, define a subfamily of DEAD-box proteins. Members from this subfamily share highly conserved protein sequences and cellular functions. They are involved in multiple steps of RNA metabolism including mRNA processing, microRNA processing, ribosome biogenesis, RNA decay, and regulation of long noncoding RNA activities. The DDX5/Dbp2 subfamily is also implicated in transcription regulation, cellular signaling pathways, and energy metabolism...
December 2, 2018: Wiley Interdisciplinary Reviews. RNA
Elodie Mailler, Jean-Christophe Paillart, Roland Marquet, Redmond P Smyth, Valerie Vivet-Boudou
RNA molecules are important players in all domains of life and the study of the relationship between their multiple flexible states and the associated biological roles has increased in recent years. For several decades, chemical and enzymatic structural probing experiments have been used to determine RNA structure. During this time, there has been a steady improvement in probing reagents and experimental methods, and today the structural biologist community has a large range of tools at its disposal to probe the secondary structure of RNAs in vitro and in cells...
November 28, 2018: Wiley Interdisciplinary Reviews. RNA
Kiyoshi Masuda, Yuki Kuwano
Gene expression patterns in cancer cells are strongly influenced by posttranscriptional mechanisms. RNA-binding proteins (RBPs) play key roles in posttranscriptional gene regulation; they can interact with target mRNAs in a sequence- and structure-dependent manner, and determine cellular behavior by manipulating the processing of these mRNAs. Numerous RBPs are aberrantly deregulated in many human cancers and hence, affect the functioning of mRNAs that encode proteins, implicated in carcinogenesis. Here, we summarize the key roles of RBPs in posttranscriptional gene regulation, describe RBPs disrupted in cancer, and lastly focus on RBPs that are responsible for implementing cancer traits in the digestive tract...
November 26, 2018: Wiley Interdisciplinary Reviews. RNA
Emilie Cerezo, Célia Plisson-Chastang, Anthony K Henras, Simon Lebaron, Pierre-Emmanuel Gleizes, Marie-Françoise O'Donohue, Yves Romeo, Yves Henry
The synthesis of ribosomal subunits in eukaryotes requires the interplay of numerous maturation and assembly factors (AFs) that intervene in the insertion of ribosomal proteins within pre-ribosomal particles, the ribosomal subunit precursors, as well as in pre-ribosomal RNA (rRNA) processing and folding. Here, we review the intricate nuclear and cytoplasmic maturation steps of pre-40S particles, the precursors to the small ribosomal subunits, in both yeast and human cells, with particular emphasis on the timing and mechanisms of AF association with and dissociation from pre-40S particles and the roles of these AFs in the maturation process...
November 8, 2018: Wiley Interdisciplinary Reviews. RNA
Nathan Meade, Stephen DiGiuseppe, Derek Walsh
Poxviruses are an unusual family of large double-stranded (ds) DNA viruses that exhibit an incredible degree of self-sufficiency and complexity in their replication and immune evasion strategies. Indeed, amongst their approximately 200 open reading frames (ORFs), poxviruses encode approximately 100 immunomodulatory proteins to counter host responses along with complete DNA synthesis, transcription, mRNA processing and cytoplasmic redox systems that enable them to replicate exclusively in the cytoplasm of infected cells...
October 31, 2018: Wiley Interdisciplinary Reviews. RNA
Erin E Duffy, Jeremy A Schofield, Matthew D Simon
Cellular RNA levels are the result of a juggling act between RNA transcription, processing, and degradation. By tuning one or more of these parameters, cells can rapidly alter the available pool of transcripts in response to stimuli. While RNA sequencing (RNA-seq) is a vital method to quantify RNA levels genome-wide, it is unable to capture the dynamics of different RNA populations at steady-state or distinguish between different mechanisms that induce changes to the steady-state (i.e., altered rate of transcription vs...
October 28, 2018: Wiley Interdisciplinary Reviews. RNA
Iain A Sawyer, David Sturgill, Miroslav Dundr
Cells are segregated into two distinct compartment groups to optimize cellular function. The first is characterized by lipid membranes that encapsulate specific regions and regulate macromolecular flux. The second, known collectively as membraneless organelles (MLOs), lacks defining lipid membranes and exhibits self-organizing properties. MLOs are enriched with specific RNAs and proteins that catalyze essential cellular processes. A prominent sub-class of MLOs are known as nuclear bodies, which includes nucleoli, paraspeckles, and other droplets...
October 25, 2018: Wiley Interdisciplinary Reviews. RNA
Christina Julius, Yulia Yuzenkova
Recently a new type of 5'-RNA cap was discovered. In contrast to the specialized eukaryotic m7 G cap, the novel caps are abundant cellular cofactors like NAD+ . RNAs capped with cofactors are found in prokaryotes and eukaryotes. Unlike m7 G cap, installed by specialized enzymes, cofactors are attached by main enzyme of transcription, RNA polymerase (RNAP). Cofactors act as noncanonical initiating substrates, provided cofactor's nucleoside base-pairs with template DNA at the transcription start site. Adenosine-containing NAD(H), flavin adenine dinucleotide (FAD), and CoA modify transcripts on promoters starting with +1A...
October 23, 2018: Wiley Interdisciplinary Reviews. RNA
Susanne Kramer, Alexander G McLennan
The 5' ends of most RNAs are chemically modified to enable protection from nucleases. In bacteria, this is often achieved by keeping the triphosphate terminus originating from transcriptional initiation, while most eukaryotic mRNAs and small nuclear RNAs have a 5'→5' linked N7 -methyl guanosine (m7 G) cap added. Several other chemical modifications have been described at RNA 5' ends. Common to all modifications is the presence of at least one pyrophosphate bond. To enable RNA turnover, these chemical modifications at the RNA 5' end need to be reversible...
October 21, 2018: Wiley Interdisciplinary Reviews. RNA
Lukas Trixl, Alexandra Lusser
It is a well-known fact that RNA is the target of a plethora of modifications which currently amount to over a hundred. The vast majority of these modifications was observed in the two most abundant classes of RNA, rRNA and tRNA. With the recent advance in mapping technologies, modifications have been discovered also in mRNA and in less abundant non-coding RNA species. These developments have sparked renewed interest in elucidating the nature and functions of those "epitransciptomic" modifications in RNA...
October 11, 2018: Wiley Interdisciplinary Reviews. RNA
Nikita Vasilyev, Ang Gao, Alexander Serganov
Although many eukaryotic transcripts contain cap structures, it has been long thought that bacterial RNAs do not carry any special modifications on their 5'-ends. In bacteria, primary transcripts are produced by transcription initiated with a nucleoside triphosphate and are therefore triphosphorylated on 5'-ends. Some transcripts are then processed by nucleases that yield monophosphorylated RNAs for specific cellular activities. Many primary transcripts are also converted to monophosphorylated species by removal of the terminal pyrophosphate for 5'-end-dependent degradation...
October 1, 2018: Wiley Interdisciplinary Reviews. RNA
Toshimichi Yamada, Nobuyoshi Akimitsu
Organisms have acquired sophisticated regulatory networks that control gene expression in response to cellular perturbations. Understanding of the mechanisms underlying the coordinated changes in gene expression in response to external and internal stimuli is a fundamental issue in biology. Recent advances in high-throughput technologies have enabled the measurement of diverse biological information, including gene expression levels, kinetics of gene expression, and interactions among gene expression regulatory molecules...
October 1, 2018: Wiley Interdisciplinary Reviews. RNA
Hong-Chao Duan, Ye Wang, Guifang Jia
N6 -methyladenosine (m6 A) is the most abundant internal chemical modification in eukaryotic messenger RNAs (mRNAs). The discovery in 2011 that m6 A is reversed by the fat mass and obesity-associated protein stimulated extensive worldwide research efforts on the regulatory biological functions of dynamic m6 A and other RNA modifications. The epitranscriptomic mark m6 A is written, read, and erased through the activities of a complicated network of enzymes and other proteins. m6 A-binding proteins read m6 A marks and transduce their downstream regulatory effects by altering RNA metabolic processes...
September 25, 2018: Wiley Interdisciplinary Reviews. RNA
Xiaolei Liu, Peter S Klein
Glycogen synthase kinase-3 (GSK-3) is a highly conserved negative regulator of receptor tyrosine kinase, cytokine, and Wnt signaling pathways. Stimulation of these pathways inhibits GSK-3 to modulate diverse downstream effectors that include transcription factors, nutrient sensors, glycogen synthesis, mitochondrial function, circadian rhythm, and cell fate. GSK-3 also regulates alternative splicing in response to T-cell receptor activation, and recent phosphoproteomic studies have revealed that multiple splicing factors and regulators of RNA biosynthesis are phosphorylated in a GSK-3-dependent manner...
November 2018: Wiley Interdisciplinary Reviews. RNA
Benjamin P Towler, Sarah F Newbury
The process of RNA degradation is a critical level of regulation contributing to the control of gene expression. In the last two decades a number of studies have shown the specific and targeted nature of RNA decay and its importance in maintaining homeostasis. The key players within the pathways of RNA decay are well conserved with their mutation or disruption resulting in distinct phenotypes as well as human disease. Model organisms including Drosophila melanogaster have played a substantial role in elucidating the mechanisms conferring control over RNA stability...
November 2018: Wiley Interdisciplinary Reviews. RNA
Jorge Cruz-Reyes, Blaine H M Mooers, Pawan K Doharey, Joshua Meehan, Shelly Gulati
RNA editing causes massive remodeling of the mitochondrial mRNA transcriptome in trypanosomes and related kinetoplastid protozoa. This type of editing involves the specific insertion or deletion of uridylates (U) directed by small noncoding guide RNAs (gRNAs). Because U-insertion exceeds U-deletion by a factor of 10, editing increases the nascent mRNA size by up to 55%. In Trypanosoma brucei, the editing apparatus uses ~40 proteins and >1,200 gRNAs to create the functional open reading frame in 12 mRNAs...
November 2018: Wiley Interdisciplinary Reviews. RNA
Manuel Garcia-Moreno, Aino I Järvelin, Alfredo Castello
The crucial participation of cellular RNA-binding proteins (RBPs) in virtually all steps of virus infection has been known for decades. However, most of the studies characterizing this phenomenon have focused on well-established RBPs harboring classical RNA-binding domains (RBDs). Recent proteome-wide approaches have greatly expanded the census of RBPs, discovering hundreds of proteins that interact with RNA through unconventional RBDs. These domains include protein-protein interaction platforms, enzymatic cores, and intrinsically disordered regions...
November 2018: Wiley Interdisciplinary Reviews. RNA
Radoslaw Pluta, Manuel Espinosa
Bacterial plasmids constitute a wealth of shared DNA amounting to about 20% of the total prokaryotic pangenome. Plasmids replicate autonomously and control their replication by maintaining a fairly constant number of copies within a given host. Plasmids should acquire a good fitness to their hosts so that they do not constitute a genetic load. Here we review some basic concepts in plasmid biology, pertaining to the control of replication and distribution of plasmid copies among daughter cells. A particular class of plasmids is constituted by those that replicate by the rolling circle mode (rolling circle-replicating [RCR]-plasmids)...
November 2018: Wiley Interdisciplinary Reviews. RNA
Graham D Pavitt
Phosphorylation of the translation initiation factor eIF2 is one of the most widely used and well-studied mechanisms cells use to respond to diverse cellular stresses. Known as the integrated stress response (ISR), the control pathway uses modulation of protein synthesis to reprogram gene expression and restore homeostasis. Here the current knowledge of the molecular mechanisms of eIF2 activation and its control by phosphorylation at a single-conserved phosphorylation site, serine 51 are discussed with a major focus on the regulatory roles of eIF2B and eIF5 where a current molecular view of ISR control of eIF2B activity is presented...
November 2018: Wiley Interdisciplinary Reviews. RNA
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