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RNA Biology

Joanne M Ho, Erol Bakkalbasi, Dieter Söll, Corwin A Miller
Inhibition of tRNA aminoacylation has proven to be an effective antimicrobial strategy, impeding an essential step of protein synthesis. Mupirocin, the well-known selective inhibitor of bacterial isoleucyl-tRNA synthetase, is one of three aminoacylation inhibitors now approved for human or animal use. However, design of novel aminoacylation inhibitors is complicated by the steadfast requirement to avoid off-target inhibition of protein synthesis in human cells. Here we review available data regarding known aminoacylation inhibitors as well as key amino-acid residues in aminoacyl-tRNA synthetases (aaRSs) and nucleotides in tRNA that determine the specificity and strength of the aaRS-tRNA interaction...
January 18, 2018: RNA Biology
Isabel Fast, David Rosenkranz
Temperature has a major impact on gene expression in ectotherms. But until recently, it was not clear in which way, if any, small non-coding RNAs such as miRNAs or piRNAs contribute to thermosensitive gene regulation. We have recently shown that temperature-responsive miRNAs in Drosophila drive adaptation to different ambient temperatures on the transcriptome level. Moreover, we demonstrated that higher temperatures lead to a more efficient piRNA-dependent transposon silencing, possibly due to heat-induced unfolding of RNA secondary structures...
January 18, 2018: RNA Biology
Ippei Sakamoto, Koichi Abe, Sumiya Kawai, Kaori Tsukakoshi, Yuta Sakai, Koji Sode, Kazunori Ikebukuro
Cyanobacteria are ideal cellular factories for biochemical production because of their ability to fix CO2 by photosynthesis and convert this molecule into biochemicals. Previously, we engineered a riboregulator that enables post-transcriptional gene regulation in the cyanobacterium Synechocystis sp. PCC 6803. Here, we improved the riboregulator by designing two RNA species, taRNA and crRNA, to enhance its induction fold. We inserted nucleotides into the crRNA loop to enhance intermolecular hybridization and successfully improved its induction fold...
January 5, 2018: RNA Biology
Cody J Wehrkamp, Sathish Kumar Natarajan, Ashley M Mohr, Mary Anne Phillippi, Justin L Mott
MicroRNA dysregulation is a common feature of cancer and due to the promiscuity of microRNA binding this can result in a wide array of genes whose expression is altered. miR-106b is an oncomiR overexpressed in cholangiocarcinoma and its upregulation in this and other cancers often leads to repression of anti-tumorigenic targets. The goal of this study was to identify the miR-106b-regulated gene landscape in cholangiocarcinoma cells using a genome-wide, unbiased mRNA analysis. Through RNA-Seq we found 112 mRNAs significantly repressed by miR-106b...
December 29, 2017: RNA Biology
Lasse Sommer Kristensen, Trine Line Hauge Okholm, Morten Trillingsgaard Venø, Jørgen Kjems
The expression patterns of endogenous circular RNA (circRNA) molecules during epidermal stem cell (EpSC) differentiation have not previously been explored. Here, we show that circRNAs are abundantly expressed in EpSCs and that their expression change dramatically during differentiation in a coordinated manner. Overall, circRNAs are expressed at higher levels in the differentiated cells, and many upregulated circRNAs are derived from developmental genes, including four different circRNAs from DLG1. The observed changes in circRNA expression were largely independent of host gene expression, and circRNAs independently upregulated upon differentiation are more prone to AGO2 binding and have more predicted miRNA binding sites compared to stably expressed circRNAs...
December 28, 2017: RNA Biology
Junjie Shi, Chunliu Huang, Shanshan Huang, Chengguo Yao
3' end processing is required for the maturation of all eukaryotic RNAs. Current model suggests that canonical mRNA 3' processing is carried out exclusively within a protein complex termed mRNA 3' processing complex. In a recent study, by using RNA-biotin based pull-down assay and high-throughput sequencing, we reported that a subset of small nucleolar RNAs (snoRNAs) were physically associated with this macromolecular machinery. Through detailed characterization of one of these snoRNAs, SNORD50A, we revealed that non-coding RNA, such as snoRNA, may play a regulatory role in mRNA 3' processing...
December 28, 2017: RNA Biology
Xiaolong Hu, Min Zhu, Xing Zhang, Bo Liu, Zi Liang, Lixu Huang, Jian Xu, Lei Yu, Kun Li, Mian Sahib Zar, Renyu Xue, Guangli Cao, Chengliang Gong
The pathogenesis of Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) infection is unclear, although accumulating evidence indicates that circular RNAs (circRNAs), which act as competing endogenous RNAs or positive regulators, play important roles in regulating gene expression in eukaryotes and, thus, may play a role in BmCPV infections. To explore the expression and biological functions of circRNAs in the silkworm midgut following BmCPV infection, silkworm circRNA expression profiles of normal midgut tissue (control) and BmCPV-infected midgut tissue (test) were determined using high-through sequencing...
December 21, 2017: RNA Biology
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No abstract text is available yet for this article.
December 20, 2017: RNA Biology
Monalisa Das, Arun Renganathan, Shrinivas Nivrutti Dighe, Utsa Bhaduri, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Manchanahalli R Satyanarayana Rao
Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions...
December 11, 2017: RNA Biology
Samuel G Rouleau, Jean-Michel Garant, François Bolduc, Martin Bisaillon, Jean-Pierre Perreault
RNA G-Quadruplexes (G4) have been shown to possess many biological functions, including the regulation of microRNA (miRNA) biogenesis and function. However, their impact on pri-miRNA processing remains unknown. We identified G4 located near the Drosha cleavage site in three distinct pri-miRNAs: pri-mir200c, pri-mir451a, and pri-mir497. The folding of the potential G4 motifs was determined in solution. Subsequently, mutations disrupting G4 folding led to important changes in the mature miRNAs levels in cells...
December 11, 2017: RNA Biology
Sinan Uğur Umu, Hilde Langseth, Cecilie Bucher-Johannessen, Bastian Fromm, Andreas Keller, Eckart Meese, Marianne Lauritzen, Magnus Leithaug, Robert Lyle, Trine B Rounge
Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA)...
December 8, 2017: RNA Biology
Ali M Yazbeck, Kifah R Tout, Peter F Stadler
The 7SK RNA is a small nuclear RNA that is involved in the regulation of Pol-II transcription. It is very well conserved in vertebrates, but shows extensive variations in both sequence and structure across invertebrates. A systematic homology search extended the collection of 7SK genes in both Arthropods and Lophotrochozoa making use of the large number of recently published invertebrate genomes. The extended data set made it possible to infer complete consensus structures for invertebrate 7SK RNAs. These show that not only the well-conserved 5'- and 3'- domains but all the interior Stem A domain is universally conserved...
December 8, 2017: RNA Biology
Victor N Ierusalimsky, Pavel M Balaban
Click-iT method can be used to trace the neurons where the newly synthesized RNA transcripts occur. Our experiments performed with the CNS of terrestrial mollusk Helix demonstrate that 5-ethynyluridine (EU) is selectively incorporated in RNA but not in DNA. The time of EU accumulation necessary for its detection was about several hours. EU was injected into the body cavity of adult mollusks, and was detectable in neurons for several days. In juveniles, EU was introduced via bathing of snails in the EU-containing saline, and was reliably detected within time period of several weeks...
December 6, 2017: RNA Biology
Anastasia McKinlay, Ram Podicheti, Jered M Wendte, Ross Cocklin, Douglas B Rusch
Nuclear multisubunit RNA polymerases IV and V (Pol IV and Pol V) evolved in plants as specialized forms of Pol II. Their functions are best understood in the context of RNA-directed DNA methylation (RdDM), a process in which Pol IV-dependent 24 nt siRNAs direct the de novo cytosine methylation of regions transcribed by Pol V. Pol V has additional functions, independent of Pol IV and 24 nt siRNA biogenesis, in maintaining the repression of transposons and genomic repeats whose silencing depends on maintenance cytosine methylation...
December 4, 2017: RNA Biology
Dooyoung Lee, Chanseok Shin
DROSHA is the catalytic subunit of the Microprocessor complex, which initiates microRNA (miRNA) maturation in the nucleus by recognizing and cleaving hairpin precursors embedded in primary transcripts. However, accumulating evidence suggests that not all hairpin substrates of DROSHA are associated with the generation of functional small RNAs. By targeting those hairpins, DROSHA regulates diverse aspects of RNA metabolism across the transcriptome, serves as a line of defense against the expression of potentially deleterious elements, and permits cell fate determination and differentiation...
November 24, 2017: RNA Biology
Christopher D Grube, Hervé Roy
Aminoacyl-tRNA synthetases (aaRSs) catalyze the aminoacylation of tRNAs to produce the aminoacyl-tRNAs (aa-tRNAs) required by ribosomes for translation of the genetic message into proteins. To ensure the accuracy of tRNA aminoacylation, and consequently the fidelity of protein synthesis, some aaRSs exhibit a proofreading (editing) site, distinct from the aa-tRNA synthetic site. The aaRS editing site hydrolyzes misacylated products formed when a non-cognate amino acid is used during tRNA charging. Because aaRSs play a central role in protein biosynthesis and cellular life, these proteins represent longstanding targets for therapeutic drug development to combat infectious diseases...
November 23, 2017: RNA Biology
Xiaokan Zhang, Shu Xiao, Rachele Dolce Rameau, Emral Devany, Zaineb Nadeem, Elif Caglar, Kenneth Ng, Frida Esther Kleiman, Anjana Saxena
Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions...
November 23, 2017: RNA Biology
Hideaki Ishikawa, Yuko Nobe, Keiichi Izumikawa, Masato Taoka, Yoshio Yamauchi, Hiroshi Nakayama, Richard J Simpson, Toshiaki Isobe, Nobuhiro Takahash
During the biogenesis of U1 small nuclear ribonucleoprotein, a small population of U1 snRNA molecules receives an extra methylation at the first transcribed nucleotide and nucleolytic cleavage to remove the 3' structured region including the Sm protein-binding site and stem-loop 4. These modifications occur before hypermethylation of the monomethylated 5' cap, and produce truncated forms of U1 snRNA (U1-tfs) that are diverted from the normal pathway to a processing body-associated degradation pathway. Here, we demonstrate that a small population of U2 snRNA molecules receives post-transcriptional modifications similar to those of U1 to yield U2-tfs...
November 23, 2017: RNA Biology
Andrés Castillo, Mario Tello, Kenneth Ringwald, Lillian G Acuña, Raquel Quatrini, Omar Orellana
Horizontal gene transfer is crucial for the adaptation of microorganisms to environmental cues. The acidophilic, bioleaching bacterium Acidithiobacillus ferrooxidans encodes an integrative-conjugative genetic element (ICEAfe1) inserted in the gene encoding a tRNA(Ala). This genetic element is actively excised from the chromosome upon induction of DNA damage. A similar genetic element (ICEAcaTY.2) is also found in an equivalent position in the genome of Acidithiobacillus caldus. The local genomic context of both mobile genetic elements is highly syntenous and the cognate integrases are well conserved...
November 23, 2017: RNA Biology
Eyal Cohen, Zohar Zafrir, Tamir Tuller
The two major steps of gene expression are transcription and translation. While hundreds of studies regarding the effect of sequence features on the translation elongation process have been published, very few connect sequence features to the transcription elongation rate. We suggest, for the first time, that short transcript sub-sequences have a typical effect on RNA polymerase (RNAP) speed: we show that nucleotide 5-mers tend to have typical RNAP speed (or transcription rate), which is consistent along different parts of genes and among different groups of genes with high correlation...
November 22, 2017: RNA Biology
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