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Wiley Interdisciplinary Reviews. RNA

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https://www.readbyqxmd.com/read/27882692/current-progress-on-micrornas-based-therapeutics-in-neurodegenerative-diseases
#1
REVIEW
Patrícia Pereira, João A Queiroz, Ana Figueiras, Fani Sousa
MicroRNAs (miRNAs)-based therapy has recently emerged as a promising strategy in the treatments of neurodegenerative diseases. Thus, in this review, the most recent and important challenges and advances on the development of miRNA therapeutics for brain targeting are discussed. In particular, this review highlights current knowledge and progress in the field of manufacturing, recovery, isolation, purification, and analysis of these therapeutic oligonucleotides. Finally, the available miRNA delivery systems are reviewed and an analysis is presented in what concerns to the current challenges that have to be addressed to ensure their specificity and efficacy...
November 24, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27873472/perfect-timing-splicing-and-transcription-rates-in-living-cells
#2
REVIEW
Tara Alpert, Lydia Herzel, Karla M Neugebauer
An important step toward understanding gene regulation is the elucidation of the time necessary for the completion of individual steps. Measurement of reaction rates can reveal potential nodes for regulation. For example, measurements of in vivo transcription elongation rates reveal regulation by DNA sequence, gene architecture, and chromatin. Pre-mRNA splicing is regulated by transcription elongation rates and vice versa, yet the rates of RNA processing reactions remain largely elusive. Since the 1980s, numerous model systems and approaches have been used to determine the precise timing of splicing in vivo...
November 21, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27863022/unwinding-the-twister-ribozyme-from-structure-to-mechanism
#3
REVIEW
Jennifer Gebetsberger, Ronald Micura
The twister ribozyme motif has been identified by bioinformatic means very recently. Currently, four crystal structures with ordered active sites together with a series of chemical and biochemical data provide insights into how this RNA accomplishes its efficient self-cleavage. Of particular interest for a mechanistic proposal are structural distinctions observed in the active sites that concern the conformation of the U-A cleavage site dinucleotide (in-line alignment of the attacking 2'-O nucleophile to the to-be-cleaved PO5' bond versus suboptimal alignments) as well as the presence/absence of Mg(2+) ions at the scissile phosphate...
November 14, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27863009/regulation-of-mrna-turnover-in-cystic-fibrosis-lung-disease
#4
REVIEW
Roopa Biswas, Parameet Kumar, Harvey B Pollard
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...
November 13, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27863061/how-to-understand-atomistic-molecular-dynamics-simulations-of-rna-and-protein-rna-complexes
#5
REVIEW
Jiří Šponer, Miroslav Krepl, Pavel Banáš, Petra Kührová, Marie Zgarbová, Petr Jurečka, Marek Havrila, Michal Otyepka
We provide a critical assessment of explicit-solvent atomistic molecular dynamics (MD) simulations of RNA and protein/RNA complexes, written primarily for non-specialists with an emphasis to explain the limitations of MD. MD simulations can be likened to hypothetical single-molecule experiments starting from single atomistic conformations and investigating genuine thermal sampling of the biomolecules. The main advantage of MD is the unlimited temporal and spatial resolution of positions of all atoms in the simulated systems...
November 10, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27863087/posttranscriptional-coordination-of-splicing-and-mirna-biogenesis-in-plants
#6
REVIEW
Agata Stepien, Katarzyna Knop, Jakub Dolata, Michal Taube, Mateusz Bajczyk, Maria Barciszewska-Pacak, Andrzej Pacak, Artur Jarmolowski, Zofia Szweykowska-Kulinska
MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play a crucial role in basic physiological and morphological processes and in response to various stresses in eukaryotic organisms. However, the miRNA biogenesis, which is based on the action of complex protein machinery, varies between plants and animals, with the differences largely concerning the location of the process, the protein composition of the microprocessor, the mechanism of miRNA action on mRNA target, and the miRNA gene ( MIR ) structure...
November 9, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27785893/new-evolutionary-insights-into-the-non-enzymatic-origin-of-rna-oligomers
#7
REVIEW
Judit E Šponer, Jiří Šponer, Ernesto Di Mauro
We outline novel findings on the non-enzymatic polymerization of nucleotides under plausible prebiotic conditions and on the spontaneous onset of informational complexity in the founding molecule, RNA. We argue that the unique ability of 3', 5' cyclic guanosine monophosphate to form stacked architectures and polymerize in a self-sustained manner suggests that this molecule may serve as the 'seed of life' from which all self-replicating oligonucleotides can be derived via a logically complete sequence of simple events...
October 26, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27748060/developmental-regulation-of-rna-processing-by-rbfox-proteins
#8
John G Conboy
The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing...
October 17, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27704722/posttranscriptional-regulation-of-intestinal-epithelial-integrity-by-noncoding-rnas
#9
Jun-Yao Wang, Lan Xiao, Jian-Ying Wang
Maintenance of the gut epithelial integrity under stressful environments requires epithelial cells to rapidly elicit changes in gene expression patterns to regulate their survival, adapt to stress, and keep epithelial homeostasis. Disruption of the intestinal epithelial integrity occurs commonly in patients with various critical illnesses, leading to the translocation of luminal toxic substances and bacteria to the blood stream. Recently, noncoding RNAs (ncRNAs) have emerged as a novel class of master regulators of gene expression and are fundamentally involved in many aspects of gut mucosal regeneration, protection, and epithelial barrier function...
October 4, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27704698/advances-in-rna-molecular-dynamics-a-simulator-s-guide-to-rna-force-fields
#10
Sweta Vangaveti, Srivathsan V Ranganathan, Alan A Chen
Molecular simulations have become an essential tool for biochemical research. When they work properly, they are able to provide invaluable interpretations of experimental results and ultimately provide novel, experimentally testable predictions. Unfortunately, not all simulation models are created equal, and with inaccurate models it becomes unclear what is a bona fide prediction versus a simulation artifact. RNA models are still in their infancy compared to the many robust protein models that are widely in use, and for that reason the number of RNA force field revisions in recent years has been rapidly increasing...
October 4, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27687155/ligand-dependent-ribozymes
#11
Michele Felletti, Jörg S Hartig
The discovery of catalytic RNA (ribozymes) more than 30 years ago significantly widened the horizon of RNA-based functions in natural systems. Similarly to the activity of protein enzymes that are often modulated by the presence of an interaction partner, some examples of naturally occurring ribozymes are influenced by ligands that can either act as cofactors or allosteric modulators. Recent discoveries of new and widespread ribozyme motifs in many different genetic contexts point toward the existence of further ligand-dependent RNA catalysts...
September 30, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27659605/rna-binding-proteins-implicated-in-neurodegenerative-diseases
#12
Mark R Cookson
Gene expression is regulated at many levels, including after generation of the primary RNA transcript from DNA but before translation into protein. Such post-translational gene regulation occurs via the action of a multitude of RNA binding proteins and include varied actions from splicing to regulation of association with the translational machinery. Primary evidence that such processes might contribute to disease mechanisms in neurodegenerative disorders comes from the observation of mutations in RNA binding proteins, particularly in diseases in the amyotrophic lateral sclerosis-frontotemporal dementia spectrum and in some forms of ataxia and tremor...
September 23, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27659427/neurodegeneration-and-rna-binding-proteins
#13
Laura De Conti, Marco Baralle, Emanuele Buratti
In the eukaryotic nucleus, RNA-binding proteins (RBPs) play a very important role in the life cycle of both coding and noncoding RNAs. As soon as they are transcribed, in fact, all RNA molecules within a cell are bound by distinct sets of RBPs that have the task of regulating its correct processing, transport, stability, and function/translation up to its final degradation. These tasks are particularly important in cells that have a complex RNA metabolism, such as neurons. Not surprisingly, therefore, recent findings have shown that the misregulation of genes involved in RNA metabolism or the autophagy/proteasome pathway plays an important role in the onset and progression of several neurodegenerative diseases...
September 22, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27620010/auf1-regulation-of-coding-and-noncoding-rna
#14
Elizabeth J F White, Aerielle E Matsangos, Gerald M Wilson
AUF1 is a family of four RNA-binding proteins (RBPs) generated by alternative pre-messenger RNA (pre-mRNA) splicing, with canonical roles in controlling the stability and/or translation of mRNA targets based on recognition of AU-rich sequences within mRNA 3' untranslated regions. However, recent studies identifying AUF1 target sites across the transcriptome have revealed that these canonical functions are but a subset of its roles in posttranscriptional regulation of gene expression. In this review, we describe recent developments in our understanding of the RNA-binding properties of AUF1 together with their biochemical implications and roles in directing mRNA decay and translation...
September 13, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27612318/emerging-roles-and-context-of-circular-rnas
#15
Amaresh C Panda, Ioannis Grammatikakis, Rachel Munk, Myriam Gorospe, Kotb Abdelmohsen
Circular RNAs (circRNAs) represent a large class of noncoding RNAs (ncRNAs) that have recently emerged as regulators of gene expression. They have been shown to suppress microRNAs, thereby increasing the translation and stability of the targets of such microRNAs. In this review, we discuss the emerging functions of circRNAs, including RNA transcription, splicing, turnover, and translation. We also discuss other possible facets of circRNAs that can influence their function depending on the cell context, such as circRNA abundance, subcellular localization, interacting partners (RNA, DNA, and proteins), dynamic changes in interactions following stimulation, and potential circRNA translation...
September 9, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27503141/advances-in-the-characterization-of-rna-binding-proteins
#16
REVIEW
Domenica Marchese, Natalia Sanchez de Groot, Nieves Lorenzo Gotor, Carmen Maria Livi, Gian G Tartaglia
From transcription, to transport, storage, and translation, RNA depends on association with different RNA-binding proteins (RBPs). Methods based on next-generation sequencing and protein mass-spectrometry have started to unveil genome-wide interactions of RBPs but many aspects still remain out of sight. How many of the binding sites identified in high-throughput screenings are functional? A number of computational methods have been developed to analyze experimental data and to obtain insights into the specificity of protein-RNA interactions...
November 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27501452/fluorophore-binding-rna-aptamers-and-their-applications
#17
Elena V Dolgosheina, Peter J Unrau
Why image RNA? Of all the biological molecules, RNA exhibits the most diverse range of functions. Evidence suggests that transcription produces a wide range of noncoding RNAs (ncRNAs), both short (e.g., siRNAs, miRNAs) and long (e.g., telomeric RNAs) that regulate many aspects of gene expression, including the epigenetic processes that underlie cell fate determination, polarization, and morphogenesis. All these functions are realized through the exquisite temporal and spatial control of RNA expression levels and the stability of specific RNAs within well-defined sub-cellular compartments...
November 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27485475/identifying-fusion-transcripts-using-next-generation-sequencing
#18
REVIEW
Shailesh Kumar, Sundus Khalid Razzaq, Angie Duy Vo, Mamta Gautam, Hui Li
Fusion transcripts (i.e., chimeric RNAs) resulting from gene fusions have been used successfully for cancer diagnosis, prognosis, and therapeutic applications. In addition, many fusion transcripts are found in normal human cell lines and tissues, with some data supporting their role in normal physiology. Besides chromosomal rearrangement, intergenic splicing can generate them. Global identification of fusion transcripts becomes possible with the help of next generation sequencing technology like RNA-Seq. In the past decade, major advancements have been made for chimeric RNA discovery due to the development of advanced sequencing platform and software packages...
November 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27444144/mrna-methylation-by-nsun2-in-cell-proliferation
#19
Wengong Wang
Methylation is a prevalent post-transcriptional modification that occurs in almost all RNA species. NSUN2, a nucleolar RNA methyltransferase, has been shown to methylate mRNAs encoding factors that control cell division and growth arrest, thereby affecting their stability and/or translation. Here, the author summarizes the recent progress in understanding NSUN2-mediated mRNA methylation and its implications in cell proliferation and senescence. WIREs RNA 2016, 7:838-842. doi: 10.1002/wrna.1380 For further resources related to this article, please visit the WIREs website...
November 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27230797/translational-regulation-in-blood-stages-of-the-malaria-parasite-plasmodium-spp-systems-wide-studies-pave-the-way
#20
Shruthi Sridhar Vembar, Dorothea Droll, Artur Scherf
The malaria parasite Plasmodium spp. varies the expression profile of its genes depending on the host it resides in and its developmental stage. Virtually all messenger RNA (mRNA) is expressed in a monocistronic manner, with transcriptional activation regulated at the epigenetic level and by specialized transcription factors. Furthermore, recent systems-wide studies have identified distinct mechanisms of post-transcriptional and translational control at various points of the parasite lifecycle. Taken together, it is evident that 'just-in-time' transcription and translation strategies coexist and coordinate protein expression during Plasmodium development, some of which we review here...
November 2016: Wiley Interdisciplinary Reviews. RNA
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