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RNA Biology

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https://www.readbyqxmd.com/read/27911188/tuning-the-ribosome-the-influence-of-rrna-modification-on-eukaryotic-ribosome-biogenesis-and-function
#1
Katherine E Sloan, Ahmed S Warda, Sunny Sharma, Karl-Dieter Entian, Denis L J Lafontaine, Markus T Bohnsack
Ribosomal RNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilise the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase centre and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27911187/fxr1a-associated-micrornp-a-driver-of-specialized-non-canonical-translation-in-quiescent-conditions
#2
Syed I A Bukhari, Shobha Vasudevan
Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth and proliferation, cells generally make their proteome via conventional translation that utilizes canonical translation factors. When faced with environmental stress such as growth factor deprivation, or in response to biological cues such as developmental signals, cells can have stalled canonical translation. In this situation, cells adapt alternative modes of translation to make specific proteins necessary for required biological functions under these distinct conditions...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27911186/rna-decay-evolution-and-the-testis
#3
Samantha H Jones, Miles Wilkinson
NMD is a highly conserved pathway that degrades specific subsets of RNAs. There is increasing evidence for roles of NMD in development. In this commentary, we focus on spermatogenesis, a process dramatically impeded upon loss or disruption of NMD. NMD requires strict regulation for normal spermatogenesis, as loss of a newly discovered NMD repressor, UPF3A, also causes spermatogenic defects, most prominently during meiosis. We discuss the unusual evolution of UPF3A, whose paralog, UPF3B, has the opposite biochemical function and acts in brain development...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27901634/detection-of-nucleic-acid-modifications-by-chemical-reagents
#4
Matthias Heiss, Stefanie Kellner
Nucleic acids, especially RNA, naturally contain a diversity of chemically modified nucleosides. To understand the biological role of these modified nucleosides, nucleic acid scientists need tools to specifically label, detect and enrich modified nucleic acids. These tools comprise a diverse set of chemical reagents which have been established in the early years of nucleic acid research. Recent developments in high-throughput sequencing and mass spectrometry utilize these chemical labeling strategies to efficiently detect and localize modifications in nucleic acids...
November 30, 2016: RNA Biology
https://www.readbyqxmd.com/read/27898262/characterization-of-genetic-loss-of-function-of-fus-in-zebrafish
#5
Svetlana Lebedeva, António M de Jesus Domingues, Falk Butter, René F Ketting
The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain...
November 29, 2016: RNA Biology
https://www.readbyqxmd.com/read/27892771/a-trna-derived-fragment-competes-with-mrna-for-ribosome-binding-and-regulates-translation-during-stress
#6
Jennifer Gebetsberger, Leander Wyss, Anna M Mleczko, Julia Reuther, Norbert Polacek
Posttranscriptional processing of RNA molecules is a common strategy to enlarge the structural and functional repertoire of RNomes observed in all three domains of life. Fragmentation of RNA molecules of basically all functional classes has been reported to yield smaller non-protein coding RNAs (ncRNAs) that typically possess different roles compared to their parental transcripts. Here we show that a valine tRNA-derived fragment (Val-tRF) that is produced under certain stress conditions in the halophilic archaeon Haloferax volcanii is capable of binding to the small ribosomal subunit...
November 28, 2016: RNA Biology
https://www.readbyqxmd.com/read/27892769/circrnas-in-the-brain
#7
Mor Hanan, Hermona Soreq, Sebastian Kadener
Circular RNAs (circRNAs) are highly abundant and evolutionarily conserved non-coding RNAs produced by circularization of specific exons. Since their re-discovery as potential regulators of gene expression, thousands of circRNAs were detected in different tissues and cell types across most organisms. Accumulating data suggest key roles for them in the central nervous system. Neuronal-expressed RNAs are diverted to yield highly enriched CircRNAs in human, mouse, pig and flies, with many of them enriched in neuronal tissues...
November 28, 2016: RNA Biology
https://www.readbyqxmd.com/read/27869537/rna-binding-to-apobec-deaminases-not-simply-a-substrate-for-c-to-u-editing
#8
Harold C Smith
Apolipoprotein B mRNA Editing Catalytic Polypeptide-like 1 or APOBEC1 was discovered in 1993 as the zinc-dependent cytidine deaminase responsible for the production of an in frame stop codon in apoB mRNA through modification of cytidine at nucleotide position 6666 to uridine. At the time of this discovery there was much speculation concerning the mechanism of base modification RNA editing which has been rekindled by the discovery of multiple C to U RNA editing events in the 3' UTRs of mRNAs and the finding that other members of the APOBEC family while able to bind RNA, have the biological function of being DNA mutating enzymes...
November 21, 2016: RNA Biology
https://www.readbyqxmd.com/read/27858580/toxins-mazf-and-mqsr-cleave-escherichia-coli-ribosomal-rna-precursors-at-multiple-sites
#9
Toomas Mets, Markus Lippus, David Schryer, Aivar Liiv, Villu Kasari, Anton Paier, Ülo Maiväli, Jaanus Remme, Tanel Tenson, Niilo Kaldalu
The endoribonuclease toxins of the E. coli toxin-antitoxin systems arrest bacterial growth and protein synthesis by targeting cellular mRNAs. As an exception, E. coli MazF was reported to cleave also 16S rRNA at a single site and separate an anti-Shine-Dalgarno sequence-containing RNA fragment from the ribosome. We noticed extensive rRNA fragmentation in response to induction of the toxins MazF and MqsR, which suggested that these toxins can cleave rRNA at multiple sites. We adapted differential RNA-sequencing to map the toxin-cleaved 5'- and 3'-ends...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27858515/eif4b-stimulates-eif4a-atpase-and-unwinding-activities-by-direct-interaction-through-its-7-repeats-region
#10
Alexandra Zoi Andreou, Ulf Harms, Dagmar Klostermeier
Eukaryotic translation initiation starts with binding of the eIF4F complex to the 5'-m7G cap of the mRNA. Recruitment of the 43S pre-initiation complex (PIC), formed by the 40S ribosomal subunit and other translation initiation factors, leads to formation of the 48S PIC that then scans the 5'-untranslated region (5'-UTR) towards the start codon. The eIF4F complex consists of eIF4E, the cap binding protein, eIF4A, a DEAD-box RNA helicase that is believed to unwind secondary structures in the 5'UTR during scanning, and eIF4G, a scaffold protein that binds to both eIF4E and eIF4A...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27858508/activation-of-transcription-enforces-the-formation-of-distinct-nuclear-bodies-in-zebrafish-embryos
#11
Patricia Heyn, Hanna Salmonowicz, Jonathan Rodenfels, Karla M Neugebauer
Nuclear bodies are cellular compartments that lack lipid bilayers and harbor specific RNAs and proteins. Recent proposals that nuclear bodies form through liquid-liquid phase separation leave the question of how different nuclear bodies maintain their distinct identities unanswered. Here we investigate Cajal bodies (CBs), histone locus bodies (HLBs) and nucleoli - involved in assembly of the splicing machinery, histone mRNA 3' end processing, and rRNA processing, respectively - in the embryos of the zebrafish, Danio rerio...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27858507/numerous-small-hammerhead-ribozyme-variants-associated-with-penelope-like-retrotransposons-cleave-rna-as-dimers
#12
Christina E Lünse, Zasha Weinberg, Ronald R Breaker
Hammerhead ribozymes represent the most common of the nine natural classes of self-cleaving RNAs. The hammerhead catalytic core includes 11 highly-conserved nucleotides located largely within the unpaired regions of a junction formed by stems I, II and III. The vast majority of previously reported examples carry an additional pseudoknot or other tertiary interactions between nucleotides that precede stem I and nucleotides in the loop of stem II. These extra contacts are critical for high-speed RNA catalysis...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#13
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27841735/cloaked-dagger-trna-slicing-by-an-unlikely-culprit
#14
Jason M Schifano, Nancy A Woychik
The unusually high number of toxin-antitoxin (TA) systems in Mycobacterium tuberculosis, the etiological agent of tuberculosis, is thought to contribute to the unique ability of this pathogen to evade killing by the immune system and persist as a latent infection. One TA family, designated mazEF (for the MazE antitoxin and MazF toxin), comprises nine of the >80 TA systems in the M. tuberculosis genome. Here we discuss the significance of our recent Nucleic Acids Res. paper that reports a surprising enzymatic activity for the MazF-mt9 toxin-sequence- and structure-specific cleavage of tRNA to generate tRNA halves-that underlies the growth-regulating properties of this toxin...
November 14, 2016: RNA Biology
https://www.readbyqxmd.com/read/27841727/atomic-mutagenesis-at-the-ribosomal-decoding-site
#15
Pius Schrode, Paul Huter, Nina Clementi, Matthias Erlacher
Ribosomal decoding is an essential process in every living cell. During protein synthesis the 30S ribosomal subunit needs to accomplish binding and accurate decoding of mRNAs. From mutational studies and high-resolution crystal structures nucleotides G530, A1492 and A1493 of the 16S ribosomal RNA came into focus as important elements for the decoding process. Recent crystallographic data challenged the so far accepted model for the decoding mechanism. To biochemically investigate decoding in greater detail we applied an in vitro reconstitution approach to modulate single chemical groups at A1492 and A1493...
November 14, 2016: RNA Biology
https://www.readbyqxmd.com/read/27841704/hiv-1-pr55-gag-binds-genomic-and-spliced-rnas-with-different-affinity-and-stoichiometry
#16
Serena Bernacchi, Ekram W Abd El-Wahab, Noé Dubois, Marcel Hijnen, Redmond P Smyth, Johnson Mak, Roland Marquet, Jean-Christophe Paillart
The HIV-1 Pr55(Gag) precursor specifically selects genomic RNA (gRNA) from a large variety of cellular and spliced viral RNAs (svRNAs), however the molecular mechanisms of this selective recognition remains poorly understood. To gain better understanding of this process, we analyzed the interactions between Pr55(Gag) and a large panel of viral RNA (vRNA) fragments encompassing the main packaging signal (Psi) and its flanking regions by fluorescence spectroscopy. We showed that the gRNA harbors a high affinity binding site which is absent from svRNA species, suggesting that this site might be crucial for selecting the HIV-1 genome...
November 14, 2016: RNA Biology
https://www.readbyqxmd.com/read/27834614/conserved-small-mrna-with-an-unique-extended-shine-dalgarno-sequence
#17
Julia Hahn, Sebastian Thalmann, Anzhela Migur, Raphael Freiherr von Boeselager, Nina Kubatova, Elena Kubareva, Harald Schwalbe, Elena Evguenieva-Hackenberg
Up to now, very small protein-coding genes have remained unrecognized in sequenced genomes. We identified an mRNA of 165 nucleotides (nt), which is conserved in Bradyrhizobiaceae and encodes a polypeptide with 14 amino acid residues (aa). The small mRNA harboring a unique Shine-Dalgarno sequence (SD) with a length of 17 nt was localized predominantly in the ribosome-containing P100 fraction of Bradyrhizobium japonicum USDA 110. Strong interaction between the mRNA and 30S ribosomal subunits was demonstrated by their co-sedimentation in sucrose density gradient...
November 11, 2016: RNA Biology
https://www.readbyqxmd.com/read/27834591/viral-interference-of-the-bacterial-rna-metabolism-machinery
#18
Tom Dendooven, An Van den Bossche, Hanne Hendrix, Pieter-Jan Ceyssens, Marleen Voe, K J Bandyra, Marc De Maeyer, Abram Aertsen, Jean-Paul Noben, Steven W Hardwick, Ben F Luisi, Rob Lavigne
In a recent publication, we reported a unique interaction between a protein encoded by the giant myovirus phiKZ and the Pseudomonas aeruginosa RNA degradosome. Crystallography, site-directed mutagenesis and interactomics approaches revealed this 'degradosome interacting protein' or Dip, to adopt an 'open-claw' dimeric structure that presents acidic patches on its outer surface which hijack two conserved RNA binding sites on the scaffold domain of the RNase E component of the RNA degradosome. This interaction prevents substrate RNAs from being bound and degraded by the RNA degradosome during the virus infection cycle...
November 11, 2016: RNA Biology
https://www.readbyqxmd.com/read/27824302/new-insights-into-the-topology-of-the-scanning-ribosome-during-translation-initiation-lessons-from-viruses
#19
René Toribio, Irene Díaz-López, Iván Ventoso
Location of the translation initiation codon generally requires scanning of the 43S ribosomal preinitiation complex (43S PIC) from the 5' of the mRNA. Associated RNA helicases can facilitate movement of the 43S PIC by removing secondary structure present in the 5' UTR of mRNA, which is required for codon inspection. The canonical RNA-dependent helicase eIF4A is directly involved in this process, as part of the eIF4F complex (eIF4G+eIF4A+eIF4E) that associates first with mRNA and then recruits the 43S PIC to initiate scanning...
November 8, 2016: RNA Biology
https://www.readbyqxmd.com/read/27819523/the-rna-methyltransferase-dnmt2-methylates-dna-in-the-structural-context-of-a-trna
#20
Steffen Kaiser, Tomasz P Jurkowski, Stefanie Kellner, Dirk Schneider, Albert Jeltsch, Mark Helm
The amino acid sequence of Dnmt2 is very similar to the catalytic domains of bacterial and eukaryotic DNA-(cytosine 5)-methyltransferases, but it efficiently catalyzes tRNA methylation, while its DNA methyltransferase activity is the subject of controversial reports with rates varying between zero and very weak. By using composite nucleic acid molecules as substrates, we surprisingly found that DNA fragments, when presented as covalent DNA-RNA hybrids in the structural context of a tRNA, can be more efficiently methylated than the corresponding natural tRNA substrate...
November 7, 2016: RNA Biology
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