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https://www.readbyqxmd.com/read/27918561/a-human-microprotein-that-interacts-with-the-mrna-decapping-complex
#1
Nadia G D'Lima, Jiao Ma, Lauren Winkler, Qian Chu, Ken H Loh, Elizabeth O Corpuz, Bogdan A Budnik, Jens Lykke-Andersen, Alan Saghatelian, Sarah A Slavoff
Proteomic detection of non-annotated microproteins indicates the translation of hundreds of small open reading frames (smORFs) in human cells, but whether these microproteins are functional or not is unknown. Here, we report the discovery and characterization of a 7-kDa human microprotein we named non-annotated P-body dissociating polypeptide (NoBody). NoBody interacts with mRNA decapping proteins, which remove the 5' cap from mRNAs to promote 5'-to-3' decay. Decapping proteins participate in mRNA turnover and nonsense-mediated decay (NMD)...
December 5, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27917860/interrogating-the-degradation-pathways-of-unstable-mrnas-with-xrn1-resistant-sequences
#2
Volker Boehm, Jennifer V Gerbracht, Marie-Charlotte Marx, Niels H Gehring
The turnover of messenger RNAs (mRNAs) is a key regulatory step of gene expression in eukaryotic cells. Due to the complexity of the mammalian degradation machinery, the contribution of decay factors to the directionality of mRNA decay is poorly understood. Here we characterize a molecular tool to interrogate mRNA turnover via the detection of XRN1-resistant decay fragments (xrFrag). Using nonsense-mediated mRNA decay (NMD) as a model pathway, we establish xrFrag analysis as a robust indicator of accelerated 5'-3' mRNA decay...
December 5, 2016: Nature Communications
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/27905550/deep-sequencing-of-transcriptome-profiling-of-gstm2-knock-down-in-swine-testis-cells
#4
Yuqi Lv, Yi Jin, Yongqiang Zhou, Jianjun Jin, Zhenfa Ma, Zhuqing Ren
Glutathione-S-transferases mu 2 (GSTM2), a kind of important Phase II antioxidant enzyme of eukaryotes, is degraded by nonsense mediated mRNA decay due to a C27T substitution in the fifth exon of pigs. As a reproductive performance-related gene, GSTM2 is involved in embryo implantation, whereas, functional deficiency of GSTM2 induces pre- or post-natal death in piglets potentially. To have some insight into the role of GSTM2 in embryo development, high throughput RNA sequencing is performed using the swine testis cells (ST) with the deletion of GSTM2...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899669/an-ultraconserved-element-uce-controls-homeostatic-splicing-of-arglu1-mrna
#5
Stephan P Pirnie, Ahmad Osman, Yinzhou Zhu, Gordon G Carmichael
Arginine and Glutamate-Rich protein 1 (ARGLU1) is a protein whose function is poorly understood, but may act in both transcription and pre-mRNA splicing. We demonstrate that the ARGLU1 gene expresses at least three distinct RNA splice isoforms - a fully spliced isoform coding for the protein, an isoform containing a retained intron that is detained in the nucleus, and an isoform containing an alternative exon that targets the transcript for nonsense mediated decay. Furthermore, ARGLU1 contains a long, highly evolutionarily conserved sequence known as an Ultraconserved Element (UCE) that is within the retained intron and overlaps the alternative exon...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899647/spliceosomal-protein-eftud2-mutation-leads-to-p53-dependent-apoptosis-in-zebrafish-neural-progenitors
#6
Lei Lei, Shou-Yu Yan, Ran Yang, Jia-Yu Chen, Yumei Li, Ye Bu, Nannan Chang, Qinchao Zhou, Xiaojun Zhu, Chuan-Yun Li, Jing-Wei Xiong
Haploinsufficiency of EFTUD2 (Elongation Factor Tu GTP Binding Domain Containing 2) is linked to human mandibulofacial dysostosis, Guion-Almeida type (MFDGA), but the underlying cellular and molecular mechanisms remain to be addressed. We report here the isolation, cloning and functional analysis of the mutated eftud2 (snu114) in a novel neuronal mutant fn10a in zebrafish. This mutant displayed abnormal brain development with evident neuronal apoptosis while the development of other organs appeared less affected...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899591/modulation-of-nonsense-mediated-decay-by-rapamycin
#7
Rocio T Martinez-Nunez, Andrew Wallace, Doyle Coyne, Linnea Jansson, Miles Rush, Hanane Ennajdaoui, Sol Katzman, Joanne Bailey, Katrin Deinhardt, Tilman Sanchez-Elsner, Jeremy R Sanford
Rapamycin is a naturally occurring macrolide whose target is at the core of nutrient and stress regulation in a wide range of species. Despite well-established roles as an inhibitor of cap-dependent mRNA translation, relatively little is known about its effects on other modes of RNA processing. Here, we characterize the landscape of rapamycin-induced post-transcriptional gene regulation. Transcriptome analysis of rapamycin-treated cells reveals genome-wide changes in alternative mRNA splicing and pronounced changes in NMD-sensitive isoforms...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27892983/association-of-mutations-in-tbk1-with-sporadic-and-familial-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#8
Axel Freischmidt, Kathrin Müller, Albert C Ludolph, Jochen H Weishaupt, Peter M Andersen
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative syndromes that occur sporadically or have been associated with mostly dominant inheritance of mutations in more than 30 genes. A critical issue is whether all reported mutations are disease causing or are coincidental findings. In this review we analyze the pathogenicity of nonsynonymous variants in the newly discovered gene encoding TANK-binding kinase 1 (TBK1). The available data suggest that mutations in TBK1 that cause a 50% reduction of TBK1 protein levels are pathogenic...
November 21, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27886048/interactions-between-the-hiv-1-unspliced-mrna-and-host-mrna-decay-machineries
#9
REVIEW
Daniela Toro-Ascuy, Bárbara Rojas-Araya, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation...
November 23, 2016: Viruses
https://www.readbyqxmd.com/read/27874031/harnessing-short-poly-a-binding-protein-interacting-peptides-for-the-suppression-of-nonsense-mediated-mrna-decay
#10
Tobias Fatscher, Niels H Gehring
Nonsense-mediated mRNA decay (NMD) is a cellular process that eliminates messenger RNA (mRNA) substrates with premature translation termination codons (PTCs). In addition, NMD regulates the expression of a number of physiological mRNAs, for example transcripts containing long 3' UTRs. Current models implicate the interaction between cytoplasmic poly(A)-binding protein (PABPC1) and translation termination in NMD. Accordingly, PABPC1 present within close proximity of a termination codon antagonizes NMD. Here, we use reporter mRNAs with different NMD-inducing 3' UTRs to establish a general NMD-inhibiting property of PABPC1...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871484/identification-of-a-nuclear-exosome-decay-pathway-for-processed-transcripts
#11
Nicola Meola, Michal Domanski, Evdoxia Karadoulama, Yun Chen, Coline Gentil, Dennis Pultz, Kristoffer Vitting-Seerup, Søren Lykke-Andersen, Jens S Andersen, Albin Sandelin, Torben Heick Jensen
The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to RNA-binding protein adaptors. One example is the trimeric human nuclear exosome targeting (NEXT) complex, which is composed of hMTR4, the Zn-finger protein ZCCHC8, and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, which demands a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the poly(A) tail exosome targeting (PAXT) connection, which comprises the ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear poly(A)-binding protein PABPN1...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27864101/targeted-exome-sequencing-identifies-novel-compound-heterozygous-mutations-in-p3h1-in-a-fetus-with-osteogenesis-imperfecta-type-viii
#12
Yanru Huang, Libin Mei, Weigang Lv, Haoxian Li, Rui Zhang, Qian Pan, Hu Tan, Jing Guo, Xiaomei Luo, Chen Chen, Desheng Liang, Lingqian Wu
Osteogenesis imperfecta (OI) is a highly clinically and genetically heterogeneous group of disorders. It is difficult to identify severe OI in the perinatal period. Here, a Chinese woman with a suspected history of fetal OI was referred to our institution at 19weeks of gestation, due to ultrasound inspection during antenatal screening, which revealed bulbous metaphyses, short humeri, and short thick bent femora in the fetus. Using targeted exome sequencing of 248 genes known to be involved in skeletal system diseases, we identified novel compound heterozygous mutation in the P3H1 gene in the fetus with OI type VIII: c...
November 15, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27859406/meeting-report-processing-translation-decay-three-ways-to-keep-rna-sizzling
#13
Albrecht G von Arnim, Hanjo A Hellmann
This meeting report highlights key trends that emerged from a conference entitled Post-Transcriptional Gene Regulation in Plants, which was held 14-15 July 2016, as a satellite meeting of the annual meeting of the American Society of Plant Biologists in Austin, Texas. The molecular biology of RNA is emerging as an integral part of the framework for plants' responses to environmental challenges such as drought and heat, hypoxia, nutrient deprivation, light and pathogens. Moreover, the conference illustrated how a multitude of customized and pioneering omics-related technologies are being applied, more and more often in combination, to describe and dissect the complexities of gene expression at the post-transcriptional level...
December 2016: Plant, Cell & Environment
https://www.readbyqxmd.com/read/27858580/toxins-mazf-and-mqsr-cleave-escherichia-coli-ribosomal-rna-precursors-at-multiple-sites
#14
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/27837180/neurogenesis-regulation-by-alternative-splicing-and-related-posttranscriptional-processes
#15
REVIEW
Enrique Lara-Pezzi, Manuel Desco, Alberto Gatto, María Victoria Gómez-Gaviro
The complexity of the mammalian brain requires highly specialized protein function and diversity. As neurons differentiate and the neuronal circuitry is established, several mRNAs undergo alternative splicing and other posttranscriptional changes that expand the variety of protein isoforms produced. Recent advances are beginning to shed light on the molecular mechanisms that regulate isoform switching during neurogenesis and the role played by specific RNA binding proteins in this process. Neurogenesis and neuronal wiring were recently shown to also be regulated by RNA degradation through nonsense-mediated decay...
November 10, 2016: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/27832540/determining-if-an-mrna-is-a-substrate-of-nonsense-mediated-mrna-decay-in-saccharomyces-cerevisiae
#16
Marcus J O Johansson
Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic quality control mechanism which triggers decay of mRNAs harboring premature translation termination codons. In this chapter, I describe methods for monitoring the influence of NMD on mRNA abundance and decay rates in Saccharomyces cerevisiae. The descriptions include detailed methods for growing yeast cells, total RNA isolation, and Northern blotting. Although the chapter focuses on NMD, the methods can be easily adapted to assess the effect of other mRNA decay pathways...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27832537/high-resolution-gene-expression-profiling-of-rna-synthesis-processing-and-decay-by-metabolic-labeling-of-newly-transcribed-rna-using-4-thiouridine
#17
Andrzej J Rutkowski, Lars Dölken
Cellular RNA levels are orchestrated by highly regulated processes involving RNA synthesis (transcription), processing (e.g., splicing, polyadenylation, transport), and degradation. Profiling these changes provides valuable information on the regulation of gene expression. Total cellular RNA is a poor template for revealing short-term changes in gene expression, alterations in RNA decay rates, and the kinetics of RNA processing as well as the differentiation thereof. Here, we describe the metabolic labeling and purification of newly transcribed RNA with 4-thiouridine, by which these limitations are overcome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27831565/a-link-between-adipogenesis-and-innate-immunity-rnase-l-promotes-3t3-l1-adipogenesis-by-destabilizing-pref-1-mrna
#18
Yi-Ting Wang, Hou-Hsien Chiang, Ying-Shing Huang, Chia-Lang Hsu, Po-Jen Yang, Hsueh-Fen Juan, Wei-Shiung Yang
Ribonuclease L (RNase-L) is an endoribonuclease well known for its roles in innate immunity. Recently it has been shown to regulate several cellular functions by modulating the levels of specific mRNAs. In this study, we investigated whether RNase-L may regulate adipocyte functions. We showed that knockdown of RNase-L reduced 3T3-L1 adipocyte differentiation and lipid accumulation. After mRNA profiling, we found that upregulation of Pref-1 mRNA, an inhibitory regulator of adipogenesis, could explain the reduced adipocyte differentiation with RNase-L downregulation...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27821608/the-role-of-ribonuclease-y-in-clostridium-perfringens-mrna-decay-and-processing
#19
Nozomu Obana, Kouji Nakamura, Nobuhiko Nomura
: Ribonuclease Y (RNase Y) is a major endoribonuclease that plays a crucial role in mRNA degradation and processing. We study the role of RNase Y in the Gram-positive anaerobic pathogen Clostridium perfringens, which has until now not been well understood. Our study implies an important role for RNase Y-mediated RNA degradation and processing in virulence gene expression and the physiological development of the organism. We began by constructing an RNase Y conditional knockdown strain in order to observe the importance of RNase Y on growth and virulence...
November 7, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27808276/post-transcriptional-gene-regulation-by-mrna-modifications
#20
Boxuan Simen Zhao, Ian A Roundtree, Chuan He
The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N(6)-methyladenosine (m(6)A) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N(6)-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses...
November 3, 2016: Nature Reviews. Molecular Cell Biology
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