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https://www.readbyqxmd.com/read/29027751/the-emerging-role-of-mrna-methylation-in-normal-and-pathological-behavior
#1
REVIEW
Mareen Engel, Alon Chen
Covalent RNA modifications were recently rediscovered as abundant RNA chemical tags. Similarly to DNA epigenetic modifications, they have been proposed as essential regulators of gene expression. Here we focus on two of the most abundant adenosine methylations: N6-methyladenosine (m(6) A), N6,2'-O-dimethyladenosine (m(6) Am) and N1-methyladenosine (m(1) A). We review the potential role of these modifications on mature mRNA in regulating gene expression within the adult brain, nervous system function and normal and pathological behavior...
October 13, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29025584/regulatory-mechanisms-of-long-noncoding-rnas-on-gene-expression-in-cancers
#2
REVIEW
Weiliang Sun, Yunben Yang, Chunjing Xu, Junming Guo
Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are non-protein coding transcripts longer than 200 nucleotides. In this review, we introduce the mechanisms by which lncRNAs regulate gene expression in four parts, epigenetic regulation (genetic imprinting and chromatin remodeling), transcriptional regulation (molecular decoy), post-transcriptional regulation (splicing and mRNA decay), and translational regulation. H19, Xist, and others are involved in genomic imprinting. HOTAIR and ANRIL function in chromatin remodeling...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29021242/autogenous-cross-regulation-of-quaking-mrna-processing-and-translation-balances-quaking-functions-in-splicing-and-translation
#3
W Samuel Fagg, Naiyou Liu, Jeffrey Haskell Fair, Lily Shiue, Sol Katzman, John Paul Donohue, Manuel Ares
Quaking protein isoforms arise from a single Quaking gene and bind the same RNA motif to regulate splicing, translation, decay, and localization of a large set of RNAs. However, the mechanisms by which Quaking expression is controlled to ensure that appropriate amounts of each isoform are available for such disparate gene expression processes are unknown. Here we explore how levels of two isoforms, nuclear Quaking-5 (Qk5) and cytoplasmic Qk6, are regulated in mouse myoblasts. We found that Qk5 and Qk6 proteins have distinct functions in splicing and translation, respectively, enforced through differential subcellular localization...
October 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/29020972/sumo1-modification-of-khsrp-regulates-tumorigenesis-by-preventing-the-tl-g-rich-mirna-biogenesis
#4
Haihua Yuan, Rong Deng, Xian Zhao, Ran Chen, Guofang Hou, Hailong Zhang, Yanli Wang, Ming Xu, Bin Jiang, Jianxiu Yu
BACKGROUND: MicroRNAs (miRNAs) are important regulators involved in diverse physiological and pathological processes including cancer. SUMO (small ubiquitin-like modifier) is a reversible protein modifier. We recently found that SUMOylation of TARBP2 and DGCR8 is involved in the regulation of the miRNA pathway. KHSRP is a single stranded nucleic acid binding protein with roles in transcription and mRNA decay, and it is also a component of the Drosha-DGCR8 complex promoting the miRNA biogenesis...
October 11, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29020934/transcriptome-analyses-reveal-sr45-to-be-a-neutral-splicing-regulator-and-a-suppressor-of-innate-immunity-in-arabidopsis-thaliana
#5
Xiao-Ning Zhang, Yifei Shi, Jordan J Powers, Nikhil B Gowda, Chong Zhang, Heba M M Ibrahim, Hannah B Ball, Samuel L Chen, Hua Lu, Stephen M Mount
BACKGROUND: Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction...
October 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29018283/codon-optimality-bias-and-usage-in-translation-and-mrna-decay
#6
REVIEW
Gavin Hanson, Jeff Coller
The advent of ribosome profiling and other tools to probe mRNA translation has revealed that codon bias - the uneven use of synonymous codons in the transcriptome - serves as a secondary genetic code: a code that guides the efficiency of protein production, the fidelity of translation and the metabolism of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a tight coupling between ribosome dynamics and the stability of mRNA transcripts; this coupling integrates codon bias into the concept of codon optimality, or the effects that specific codons and tRNA concentrations have on the efficiency and fidelity of the translation machinery...
October 11, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28993941/il-8-is-involved-in-estrogen-related-receptor-%C3%AE-regulated-proliferation-and-migration-of-colorectal-cancer-cells
#7
Sijuan Ding, Zhaohui Tang, Yongjun Jiang, Honglin Huang, Pengfei Luo, Bohua Qing, Siyuan Zhang, Ruoting Tang
BACKGROUND AND AIMS: Studies revealed that estrogenic signals were involved in the development of colorectal cancer (CRC), while the roles of estrogen related receptor (ERR) on the progression of CRC have not been well illustrated. Its roles on the development of CRC were investigated. METHODS: The expression of ERRα/β/γ in CRC cells were measured. The effects of ERRα on cell proliferation, migration and expression of cytokines were investigated accordingly...
October 9, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28985509/untangling-p-bodies-dissecting-the-complex-web-of-interactions-that-enable-tiered-control-of-gene-expression
#8
Christopher J Kershaw, Mark P Ashe
In this issue of Molecular Cell, Hubstenberger et al. (2017) define the molecular composition of P-bodies isolated from human epithelial cells to propose that these foci act as mRNA storage depots rather than mRNA decay facilities.
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28984438/engineering-the-genetic-code-in-cells-and-animals-biological-considerations-and-impacts
#9
Lei Wang
Expansion of the genetic code allows unnatural amino acids (Uaas) to be site-specifically incorporated into proteins in live biological systems, thus enabling novel properties selectively introduced into target proteins in vivo for basic biological studies and for engineering of novel biological functions. Orthogonal components including tRNA and aminoacyl-tRNA synthetase (aaRS) are expressed in live cells to decode a unique codon (often the amber stop codon UAG) as the desired Uaa. Initially developed in E...
October 6, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28984054/rna-uridylation-a-key-posttranscriptional-modification-shaping-the-coding-and-noncoding-transcriptome
#10
REVIEW
Caroline De Almeida, Hélène Scheer, Hélène Zuber, Dominique Gagliardi
RNA uridylation is a potent and widespread posttranscriptional regulator of gene expression. RNA uridylation has been detected in a range of eukaryotes including trypanosomes, animals, plants, and fungi, but with the noticeable exception of budding yeast. Virtually all classes of eukaryotic RNAs can be uridylated and uridylation can also tag viral RNAs. The untemplated addition of a few uridines at the 3' end of a transcript can have a decisive impact on RNA's fate. In rare instances, uridylation is an intrinsic step in the maturation of noncoding RNAs like for the U6 spliceosomal RNA or mitochondrial guide RNAs in trypanosomes...
October 5, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28983119/the-gbap1-pseudogene-acts-as-a-cerna-for-the-glucocerebrosidase-gene-gba-by-sponging-mir-22-3p
#11
Letizia Straniero, Valeria Rimoldi, Maura Samarani, Stefano Goldwurm, Alessio Di Fonzo, Rejko Krüger, Michela Deleidi, Massimo Aureli, Giulia Soldà, Stefano Duga, Rosanna Asselta
Mutations in the GBA gene, encoding lysosomal glucocerebrosidase, represent the major predisposing factor for Parkinson's disease (PD), and modulation of the glucocerebrosidase activity is an emerging PD therapy. However, little is known about mechanisms regulating GBA expression. We explored the existence of a regulatory network involving GBA, its expressed pseudogene GBAP1, and microRNAs. The high level of sequence identity between GBA and GBAP1 makes the pseudogene a promising competing-endogenous RNA (ceRNA), functioning as a microRNA sponge...
October 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28977534/fractionation-iclip-detects-persistent-sr-protein-binding-to-conserved-retained-introns-in-chromatin-nucleoplasm-and-cytoplasm
#12
Mattia Brugiolo, Valentina Botti, Na Liu, Michaela Müller-McNicoll, Karla M Neugebauer
RNA binding proteins (RBPs) regulate the lives of all RNAs from transcription, processing, and function to decay. How RNA-protein interactions change over time and space to support these roles is poorly understood. Towards this end, we sought to determine how two SR proteins-SRSF3 and SRSF7, regulators of pre-mRNA splicing, nuclear export and translation-interact with RNA in different cellular compartments. To do so, we developed Fractionation iCLIP (Fr-iCLIP), in which chromatin, nucleoplasmic and cytoplasmic fractions are prepared from UV-crosslinked cells and then subjected to iCLIP...
August 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28970560/endogenous-mirna-in-the-green-alga-chlamydomonas-regulates-gene-expression-through-cds-targeting
#13
Betty Y-W Chung, Michael J Deery, Arnoud J Groen, Julie Howard, David C Baulcombe
MicroRNAs (miRNAs) are 21-24-nucleotide RNAs present in many eukaryotes that regulate gene expression as part of the RNA-induced silencing complex. The sequence identity of the miRNA provides the specificity to guide the silencing effector Argonaute (AGO) protein to target mRNAs via a base-pairing process (1) . The AGO complex promotes translation repression and/or accelerated decay of this target mRNA (2) . There is overwhelming evidence both in vivo and in vitro that translation repression plays a major role (3-7) ...
October 2, 2017: Nature Plants
https://www.readbyqxmd.com/read/28965817/p-body-purification-reveals-the-condensation-of-repressed-mrna-regulons
#14
Arnaud Hubstenberger, Maïté Courel, Marianne Bénard, Sylvie Souquere, Michèle Ernoult-Lange, Racha Chouaib, Zhou Yi, Jean-Baptiste Morlot, Annie Munier, Magali Fradet, Maëlle Daunesse, Edouard Bertrand, Gérard Pierron, Julien Mozziconacci, Michel Kress, Dominique Weil
Within cells, soluble RNPs can switch states to coassemble and condense into liquid or solid bodies. Although these phase transitions have been reconstituted in vitro, for endogenous bodies the diversity of the components, the specificity of the interaction networks, and the function of the coassemblies remain to be characterized. Here, by developing a fluorescence-activated particle sorting (FAPS) method to purify cytosolic processing bodies (P-bodies) from human epithelial cells, we identified hundreds of proteins and thousands of mRNAs that structure a dense network of interactions, separating P-body from non-P-body RNPs...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28965759/temporal-control-of-mammalian-cortical-neurogenesis-by-m-6-a-methylation
#15
Ki-Jun Yoon, Francisca Rojas Ringeling, Caroline Vissers, Fadi Jacob, Michael Pokrass, Dennisse Jimenez-Cyrus, Yijing Su, Nam-Shik Kim, Yunhua Zhu, Lily Zheng, Sunghan Kim, Xinyuan Wang, Louis C Doré, Peng Jin, Sergi Regot, Xiaoxi Zhuang, Stefan Canzar, Chuan He, Guo-Li Ming, Hongjun Song
N(6)-methyladenosine (m(6)A), installed by the Mettl3/Mettl14 methyltransferase complex, is the most prevalent internal mRNA modification. Whether m(6)A regulates mammalian brain development is unknown. Here, we show that m(6)A depletion by Mettl14 knockout in embryonic mouse brains prolongs the cell cycle of radial glia cells and extends cortical neurogenesis into postnatal stages. m(6)A depletion by Mettl3 knockdown also leads to a prolonged cell cycle and maintenance of radial glia cells. m(6)A sequencing of embryonic mouse cortex reveals enrichment of mRNAs related to transcription factors, neurogenesis, the cell cycle, and neuronal differentiation, and m(6)A tagging promotes their decay...
September 25, 2017: Cell
https://www.readbyqxmd.com/read/28964725/how-mirs-and-mrna-deadenylases-could-post-transcriptionally-regulate-expression-of-tumor-promoting-protein-pld
#16
REVIEW
Julian Gomez-Cambronero, Kristen Fite, Taylor E Miller
Phospholipase D (PLD) plays a key role in both cell membrane lipid reorganization and architecture, as well as a cell signaling protein via the product of its enzymatic reaction, phosphatidic acid (PA). PLD is involved in promoting breast cancer cell growth, proliferation, and metastasis and both gene and protein expression are upregulated in breast carcinoma human samples. In spite of all this, the ultimate reason as to why PLD expression is high in cancer cells vs. their normal counterparts remains largely unknown...
August 24, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28959040/endoplasmic-reticulum-stress-preconditioning-modifies-intracellular-mercury-content-by-upregulating-membrane-transporters
#17
Fusako Usuki, Masatake Fujimura, Akio Yamashita
Endoplasmic reticulum (ER) stress preconditioning protects cells against methylmercury (MeHg) cytotoxicity by inducing integrated stress responses such as eIF2α phosphorylation, ATF4 accumulation, and nonsense-mediated mRNA decay (NMD) suppression. Here we demonstrated that ER stress preconditioning results in the upregulation of membrane transporters, leading to a decrease in intracellular mercury content. Our analyses showed that ER stress preconditioning upregulated the expression of methionine transporters that affect the cellular influx of MeHg, LAT1, LAT3, and SNAT2; and a membrane transporter that affects the efflux of MeHg, ABCC4, in MeHg-susceptible myogenic cells...
September 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28956756/asc1-and-rps3-new-actors-in-18s-non-functional-rrna-decay
#18
Kelly A Limoncelli, Christopher N Merrikh, Melissa J Moore
In budding yeast, inactivating mutations within the 40S ribosomal subunit decoding center lead to 18S rRNA clearance by a quality control mechanism known as nonfunctional 18S rRNA decay (18S NRD). We previously showed that 18S NRD is functionally related to No-Go mRNA Decay (NGD), a pathway for clearing translation complexes stalled on aberrant mRNAs. Whereas the NGD factors DOM34 and HBS1 contribute to 18S NRD, their genetic deletion (either singly or in combination) only partially stabilizes mutant 18S rRNA...
September 27, 2017: RNA
https://www.readbyqxmd.com/read/28952924/unfolded-protein-response-transducer-ire1-mediated-signaling-independent-of-xbp1-mrna-splicing-is-not-required-for-growth-and-development-of-medaka-fish
#19
Tokiro Ishikawa, Makoto Kashima, Atsushi J Nagano, Tomoko Ishikawa-Fujiwara, Yasuhiro Kamei, Takeshi Todo, Kazutoshi Mori
When activated by the accumulation of unfolded proteins in the endoplasmic reticulum, metazoan IRE1, the most evolutionarily conserved unfolded protein response (UPR) transducer, initiates unconventional splicing of XBP1 mRNA. Unspliced and spliced mRNA are translated to produce pXBP1(U) and pXBP1(S), respectively. pXBP1(S) functions as a potent transcription factor, whereas pXBP1(U) targets pXBP1(S) to degradation. In addition, activated IRE1 transmits two signaling outputs independent of XBP1, namely activation of the JNK pathway, which is initiated by binding of the adaptor TRAF2 to phosphorylated IRE1, and regulated IRE1-dependent decay (RIDD) of various mRNAs in a relatively nonspecific manner...
September 27, 2017: ELife
https://www.readbyqxmd.com/read/28950212/p-val19glyfs-21-and-p-leu228-variants-in-the-survival-of-motor-neuron-1-trigger-nonsense-mediated-mrna-decay-causing-the-smn1-ptc-transcripts-degradation
#20
Yu-Jin Qu, Lin Ge, Jin-Li Bai, Yan-Yan Cao, Yu-Wei Jin, Hong Wang, Lan Yang, Fang Song
Spinal Muscular Atrophy (SMA) results from loss-of-function mutations in the survival of motor neuron 1 (SMN1) gene. Our previous research showed that 40% of variants were nonsense or frameshift variants and SMN1 mRNA levels in the patients carrying these variants were significantly decreased. Here we selected one rare variant (p.Val19Glyfs*21) and one common variant (p.Leu228*) to explore the degradation mechanism of mutant transcripts. The levels of full-length (FL)-SMN1 transcripts and SMN protein in the cell lines from the patients with these variants were both significantly reduced (p<0...
September 15, 2017: Mutation Research
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