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https://www.readbyqxmd.com/read/28096443/stem-loop-rna-labeling-can-affect-nuclear-and-cytoplasmic-mrna-processing
#1
Stephanie Heinrich, Corinne L Sidler, Claus M Azzalin, Karsten Weis
The binding of sequence-specific RNA-interacting proteins, such as the bacteriophage MS2 or PP7 coat proteins, to their corresponding target sequences has been extremely useful and widely used to visualize single mRNAs in vivo. However, introduction of MS2 stem-loops into yeast mRNAs has recently been shown to lead to the accumulation of RNA fragments, suggesting that the loops impair mRNA decay. This result was questioned, because fragment occurrence was mainly assessed using ensemble methods, and their cellular localization and its implications had not been addressed on a single transcript level...
February 2017: RNA
https://www.readbyqxmd.com/read/28096332/human-nf-%C3%AE%C2%BAb-repressing-factor-acts-as-a-stress-regulated-switch-for-ribosomal-rna-processing-and-nucleolar-homeostasis-surveillance
#2
Marta Coccia, Antonio Rossi, Anna Riccio, Edoardo Trotta, Maria Gabriella Santoro
The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the master regulator of stress-induced transcriptional responses, controls the expression of cytoprotective heat shock proteins (HSPs), molecular chaperones/cochaperones constituting a major component of the cell protein quality control machinery essential to circumvent stress-induced degradation and aggregation of misfolded proteins...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095098/reduced-penetrance-in-a-large-caucasian-pedigree-with-stickler-syndrome
#3
Stuart W Tompson, Charles Johnson, Diana Abbott, Benjamin Bakall, Vincent Soler, Tammy L Yanovitch, Kristina N Whisenhunt, Thomas Klemm, Steve Rozen, Edwin M Stone, Max Johnson, Terri L Young
BACKGROUND: In a four-generation Caucasian family variably diagnosed with autosomal dominant (AD) Stickler or Wagner disease, commercial gene screening failed to identify a mutation in COL2A1 or VCAN. We utilized linkage mapping and exome sequencing to identify the causal variant. MATERIALS AND METHODS: Genomic DNA samples collected from 40 family members were analyzed. A whole-genome linkage scan was performed using Illumina HumanLinkage-24 BeadChip followed by two-point and multipoint linkage analyses using FASTLINK and MERLIN...
January 17, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28090303/genotype-phenotype-effects-of-bmpr2-mutations-on-disease-severity-in-mouse-models-of-pulmonary-hypertension
#4
Andrea L Frump, Arunima Datta, Sampa Ghose, James West, Mark P de Caestecker
More than 350 mutations in the type-2 BMP (bone morphogenetic protein) receptor, BMPR2, have been identified in patients with heritable pulmonary arterial hypertension (HPAH). However, only 30% of BMPR2 mutation carriers develop PAH, and we cannot predict which of these carriers will develop clinical disease. One possibility is that the nature of the BMPR2 mutation affects disease severity. This hypothesis has been difficult to test clinically, given the rarity of HPAH and the complexity of the confounding genetic and environmental risk factors...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28088137/forces-on-nuclei-moving-on-autoionizing-molecular-potential-energy-surfaces
#5
Nimrod Moiseyev
Autoionization of molecular systems occurs in diatomic molecules and in small biochemical systems. Quantum chemistry packages enable calculation of complex potential energy surfaces (CPESs). The imaginary part of the CPES is associated with the autoionization decay rate, which is a function of the molecular structure. Molecular dynamics simulations, within the framework of the Born-Oppenheimer approximation, require the definition of a force field. The ability to calculate the forces on the nuclei in bio-systems when autoionization takes place seems to rely on an understanding of radiative damages in RNA and DNA arising from the release of slow moving electrons which have long de Broglie wavelengths...
January 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28073787/col6a5-variants-in-familial-neuropathic-chronic-itch
#6
Filippo Martinelli-Boneschi, Marina Colombi, Marco Castori, Grazia Devigili, Roberto Eleopra, Rayaz A Malik, Marco Ritelli, Nicoletta Zoppi, Chiara Dordoni, Melissa Sorosina, Paola Grammatico, Hassan Fadavi, Monique M Gerrits, Rowida Almomani, Catharina G Faber, Ingemar S J Merkies, Daniela Toniolo, Massimiliano Cocca, Claudio Doglioni, Stephen G Waxman, Sulayman D Dib-Hajj, Michela M Taiana, Jenny Sassone, Raffaella Lombardi, Daniele Cazzato, Andrea Zauli, Silvia Santoro, Margherita Marchi, Giuseppe Lauria
Itch is thought to represent the peculiar response to stimuli conveyed by somatosensory pathways shared with pain through the activation of specific neurons and receptors. It can occur in association with dermatological, systemic and neurological diseases, or be the side effect of certain drugs. However, some patients suffer from chronic idiopathic itch that is frequently ascribed to psychological distress and for which no biomarker is available to date. We investigated three multigenerational families, one of which diagnosed with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), characterized by idiopathic chronic itch with predominantly proximal distribution...
January 9, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28059081/aba-unresponsive-snrk2-protein-kinases-regulate-mrna-decay-under-osmotic-stress-in-plants
#7
Fumiyuki Soma, Junro Mogami, Takuya Yoshida, Midori Abekura, Fuminori Takahashi, Satoshi Kidokoro, Junya Mizoi, Kazuo Shinozaki, Kazuko Yamaguchi-Shinozaki
Rapid changes in messenger RNA population are vital for plants to properly exert multiple adaptive responses under continuously changing stress conditions. Transcriptional activation mediated by the 'abscisic acid (ABA)-activated SnRK2 protein kinases-ABA-responsive element (ABRE)-binding proteins/ABRE-binding factors (AREB/ABFs)' signalling module is a crucial step in the expression of stress-inducible genes under osmotic stress conditions in Arabidopsis(1-4). In addition to transcriptional control, proper transcript levels of individual genes can be achieved by post-transcriptional regulation, but how this regulation functions under stress conditions and the underlying molecular mechanisms remain elusive...
January 6, 2017: Nature Plants
https://www.readbyqxmd.com/read/28054965/attacked-from-all-sides-rna-decay-in-antiviral-defense
#8
REVIEW
Jerome M Molleston, Sara Cherry
The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5' or 3' end, is increasingly recognized as playing an important role in antiviral defense. The 5' degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs...
January 4, 2017: Viruses
https://www.readbyqxmd.com/read/28053121/adar2-regulates-rna-stability-by-modifying-access-of-decay-promoting-rna-binding-proteins
#9
Aparna Anantharaman, Vidisha Tripathi, Abid Khan, Je-Hyun Yoon, Deepak K Singh, Omid Gholamalamdari, Shuomeng Guang, Johan Ohlson, Helene Wahlstedt, Marie Öhman, Michael F Jantsch, Nicholas K Conrad, Jian Ma, Myriam Gorospe, Supriya G Prasanth, Kannanganattu V Prasanth
Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3'UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28027311/somatic-mutation-patterns-in-hemizygous-genomic-regions-unveil-purifying-selection-during-tumor-evolution
#10
Jimmy Van den Eynden, Swaraj Basu, Erik Larsson
Identification of cancer driver genes using somatic mutation patterns indicative of positive selection has become a major goal in cancer genomics. However, cancer cells additionally depend on a large number of genes involved in basic cellular processes. While such genes should in theory be subject to strong purifying (negative) selection against damaging somatic mutations, these patterns have been elusive and purifying selection remains inadequately explored in cancer. Here, we hypothesized that purifying selection should be evident in hemizygous genomic regions, where damaging mutations cannot be compensated for by healthy alleles...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/28011790/high-throughput-interpretation-of-gene-structure-changes-in-human-and-nonhuman-resequencing-data-using-ace
#11
William H Majoros, Michael S Campbell, Carson Holt, Erin DeNardo, Doreen Ware, Andrew S Allen, Mark Yandell, Timothy E Reddy
MOTIVATION: The accurate interpretation of genetic variants is critical for characterizing genotype-phenotype associations. Because the effects of genetic variants can depend strongly on their local genomic context, accurate genome annotations are essential. Furthermore, as some variants have the potential to disrupt or alter gene structure, variant interpretation efforts stand to gain from the use of individualized annotations that account for differences in gene structure between individuals or strains...
December 23, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28011423/mrna-decay-in-plants-both-quantity-and-quality-matter
#12
REVIEW
Xinyan Zhang, Hongwei Guo
In eukaryotes, degradation of messenger RNAs (mRNAs) is required for both mRNA quantity and quality control. Fine-tuning of the abundance of mRNAs that are to be translated can be achieved through a deadenylation-mediated RNA decay pathway involving progressive removal of poly(A) tails, decapping and exoribonuclease digestion. While the classical view assumes that mRNAs are degraded only after their exit from protein translation, recent studies have revealed mRNA decay can occur during translation in plants...
December 20, 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28009841/use-of-cellular-decapping-activators-by-positive-strand-rna-viruses
#13
REVIEW
Jennifer Jungfleisch, Bernat Blasco-Moreno, Juana Díez
Positive-strand RNA viruses have evolved multiple strategies to not only circumvent the hostile decay machinery but to trick it into being a priceless collaborator supporting viral RNA translation and replication. In this review, we describe the versatile interaction of positive-strand RNA viruses and the 5'-3' mRNA decay machinery with a focus on the viral subversion of decapping activators. This highly conserved viral trickery is exemplified with the plant Brome mosaic virus, the animal Flock house virus and the human hepatitis C virus...
December 21, 2016: Viruses
https://www.readbyqxmd.com/read/28008922/atp-hydrolysis-by-upf1-is-required-for-efficient-translation-termination-at-premature-stop-codons
#14
Lucas D Serdar, DaJuan L Whiteside, Kristian E Baker
Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon...
December 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/28008748/tbk1-mutation-spectrum-in-an-extended-european-patient-cohort-with-frontotemporal-dementia-and-amyotrophic-lateral-sclerosis
#15
Julie van der Zee, Ilse Gijselinck, Sara Van Mossevelde, Federica Perrone, Lubina Dillen, Bavo Heeman, Veerle Bäumer, Sebastiaan Engelborghs, Jan De Bleecker, Jonathan Baets, Ellen Gelpi, Ricardo Rojas-García, Jordi Clarimón, Alberto Lleó, Janine Diehl-Schmid, Panagiotis Alexopoulos, Robert Perneczky, Matthis Synofzik, Jennifer Just, Ludger Schöls, Caroline Graff, Håkan Thonberg, Barbara Borroni, Alessandro Padovani, Albena Jordanova, Stayko Sarafov, Ivailo Tournev, Alexandre de Mendonça, Gabriel Miltenberger-Miltényi, Frederico Simões do Couto, Alfredo Ramirez, Frank Jessen, Michael T Heneka, Estrella Gómez-Tortosa, Adrian Danek, Patrick Cras, Rik Vandenberghe, Peter De Jonghe, Peter P De Deyn, Kristel Sleegers, Marc Cruts, Christine Van Broeckhoven, Johan Goeman, Dirk Nuytten, Katrien Smets, Wim Robberecht, Philip Van Damme, Jan De Bleecker, Patrick Santens, Bart Dermaut, Jan Versijpt, Alex Michotte, Adrian Ivanoiu, Olivier Deryck, Bruno Bergmans, Jean Delbeck, Marc Bruyland, Christiana Willems, Eric Salmon, Pau Pastor, Sara Ortega-Cubero, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Isabel Hernández, Mercè Boada, Agustín Ruiz, Sandro Sorbi, Benedetta Nacmias, Silvia Bagnoli, Sandro Sorbi, Raquel Sanchez-Valle, Albert Llado, Isabel Santana, Maria Rosário Almeida, Giovanni B Frisoni, Walter Maetzler, Radoslav Matej, Matthew J Fraidakis, Gabor G Kovacs, Gian Maria Fabrizi, Silvia Testi
We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1...
December 23, 2016: Human Mutation
https://www.readbyqxmd.com/read/28008720/the-exon-junction-complex-a-lifelong-guardian-of-mrna-fate
#16
REVIEW
Lauren A Woodward, Justin W Mabin, Pooja Gangras, Guramrit Singh
During messenger RNA (mRNA) biogenesis and processing in the nucleus, many proteins are imprinted on mRNAs assembling them into messenger ribonucleoproteins (mRNPs). Some of these proteins remain stably bound within mRNPs and have a long-lasting impact on their fate. One of the best-studied examples is the exon junction complex (EJC), a multiprotein complex deposited primarily 24 nucleotides upstream of exon-exon junctions as a consequence of pre-mRNA splicing. The EJC maintains a stable, sequence-independent, hold on the mRNA until its removal during translation in the cytoplasm...
December 23, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27999393/diverse-strategies-used-by-picornaviruses-to-escape-host-rna-decay-pathways
#17
REVIEW
Wendy Ullmer, Bert L Semler
To successfully replicate, viruses protect their genomic material from degradation by the host cell. RNA viruses must contend with numerous destabilizing host cell processes including mRNA decay pathways and viral RNA (vRNA) degradation resulting from the antiviral response. Members of the Picornaviridae family of small RNA viruses have evolved numerous diverse strategies to evade RNA decay, including incorporation of stabilizing elements into vRNA and re-purposing host stability factors. Viral proteins are deployed to disrupt and inhibit components of the decay machinery and to redirect decay machinery to the advantage of the virus...
December 20, 2016: Viruses
https://www.readbyqxmd.com/read/27995867/poly-a-polymerase-i-participates-in-the-indole-regulatory-pathway-of-pantoea-agglomerans-ys19
#18
Zihua Li, Jing Jiang, Xuemei Yu, Cunxiang Wu, Delong Shen, Yongjun Feng
Pantoea agglomerans YS19 is a preponderant endophytic bacterium isolated from rice. It is characterized by the formation of symplasmata, a type of multicellular aggregate structure, contributing to a strong stress-resistance and specific adaptation of YS19 in endophyte-host associations. Indole is an important signal molecule in intraspecies or interspecies relationships, regulating a variety of bacterial behaviors such as cell aggregation and stress-resistance; however, the regulatory mechanism remains an on-going area of investigation...
December 20, 2016: Microbiology
https://www.readbyqxmd.com/read/27994032/rapid-decay-of-engulfed-extracellular-mirna-by-xrn1-exonuclease-promotes-transient-epithelial-mesenchymal-transition
#19
Joséphine Zangari, Marius Ilie, Florian Rouaud, Laurie Signetti, Mickaël Ohanna, Robin Didier, Barnabé Roméo, Dana Goldoni, Nicolas Nottet, Cathy Staedel, Jocelyn Gal, Bernard Mari, Baharia Mograbi, Paul Hofman, Patrick Brest
Extracellular vesicles (EVs) have been shown to play an important role in intercellular communication as carriers of DNA, RNA and proteins. While the intercellular transfer of miRNA through EVs has been extensively studied, the stability of extracellular miRNA (ex-miRNA) once engulfed by a recipient cell remains to be determined. Here, we identify the ex-miRNA-directed phenotype to be transient due to the rapid decay of ex-miRNA. We demonstrate that the ex-miR-223-3p transferred from polymorphonuclear leukocytes to cancer cells were functional, as demonstrated by the decreased expression of its target FOXO1 and the occurrence of epithelial-mesenchymal transition reprogramming...
December 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27991510/rna-decay-nobody-binds-to-mrna-decapping-proteins
#20
Kim Baumann
No abstract text is available yet for this article.
December 19, 2016: Nature Reviews. Molecular Cell Biology
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