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https://www.readbyqxmd.com/read/29610251/corrigendum-transcription-rate-strongly-affects-splicing-fidelity-and-cotranscriptionality-in-budding-yeast
#1
Vahid Aslanzadeh, Yuanhua Huang, Guido Sanguinetti, Jean D Beggs
No abstract text is available yet for this article.
April 2018: Genome Research
https://www.readbyqxmd.com/read/29483154/transcription-elongation-rate-affects-nascent-histone-pre-mrna-folding-and-3-end-processing
#2
Tassa Saldi, Nova Fong, David L Bentley
Transcription elongation rate influences cotranscriptional pre-mRNA maturation, but how such kinetic coupling works is poorly understood. The formation of nonadenylated histone mRNA 3' ends requires recognition of an RNA structure by stem-loop-binding protein (SLBP). We report that slow transcription by mutant RNA polymerase II (Pol II) caused accumulation of polyadenylated histone mRNAs that extend past the stem-loop processing site. UV irradiation, which decelerates Pol II elongation, also induced long poly(A)+ histone transcripts...
February 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29432121/xrn2-accelerates-termination-by-rna-polymerase-ii-which-is-underpinned-by-cpsf73-activity
#3
Joshua D Eaton, Lee Davidson, David L V Bauer, Toyoaki Natsume, Masato T Kanemaki, Steven West
Termination is a ubiquitous phase in every transcription cycle but is incompletely understood and a subject of debate. We used gene editing as a new approach to address its mechanism through engineered conditional depletion of the 5' → 3' exonuclease Xrn2 or the polyadenylation signal (PAS) endonuclease CPSF73 (cleavage and polyadenylation specificity factor 73). The ability to rapidly control Xrn2 reveals a clear and general role for it in cotranscriptional degradation of 3' flanking region RNA and transcriptional termination...
January 15, 2018: Genes & Development
https://www.readbyqxmd.com/read/29311329/dysregulation-of-cotranscriptional-alternative-splicing-underlies-charge-syndrome
#4
Catherine Bélanger, Félix-Antoine Bérubé-Simard, Elizabeth Leduc, Guillaume Bernas, Philippe M Campeau, Seema R Lalani, Donna M Martin, Stephanie Bielas, Amanda Moccia, Anshika Srivastava, David W Silversides, Nicolas Pilon
CHARGE syndrome-which stands for coloboma of the eye, heart defects, atresia of choanae, retardation of growth/development, genital abnormalities, and ear anomalies-is a severe developmental disorder with wide phenotypic variability, caused mainly by mutations in CHD7 (chromodomain helicase DNA-binding protein 7), known to encode a chromatin remodeler. The genetic lesions responsible for CHD7 mutation-negative cases are unknown, at least in part because the pathogenic mechanisms underlying CHARGE syndrome remain poorly defined...
January 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29311227/src-and-confinement-dependent-fak-activation-causes-e-cadherin-relaxation-and-%C3%AE-catenin-activity
#5
Charlène Gayrard, Clément Bernaudin, Théophile Déjardin, Cynthia Seiler, Nicolas Borghi
In epithelia, E-cadherin cytoplasmic tail is under cytoskeleton-generated tension via a link that contains β-catenin. A cotranscription factor, β-catenin, is also active in morphogenetic processes associated with epithelial-to-mesenchymal transition. β-Catenin signaling appears mechanically inducible and was proposed to follow phosphorylation-induced β-catenin release from E-cadherin. Evidence for this mechanism is lacking, and whether E-cadherin tension is involved is unknown. To test this, we combined quantitative fluorescence microscopies with genetic and pharmacological perturbations of epithelial-to-mesenchymal transition-induced cells in culture...
March 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29279370/single-molecule-fret-studies-on-the-cotranscriptional-folding-of-a-thiamine-pyrophosphate-riboswitch
#6
Heesoo Uhm, Wooyoung Kang, Kook Sun Ha, Changwon Kang, Sungchul Hohng
Because RNAs fold as they are being synthesized, their transcription rate can affect their folding. Here, we report the results of single-molecule fluorescence studies that characterize the ligand-dependent cotranscriptional folding of the Escherichia coli thiM riboswitch that regulates translation. We found that the riboswitch aptamer folds into the "off" conformation independent of its ligand, but switches to the "on" conformation during transcriptional pausing near the translational start codon...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29237752/ser7-of-rnapii-ctd-facilitates-heterochromatin-formation-by-linking-ncrna-to-rnai
#7
Takuya Kajitani, Hiroaki Kato, Yuji Chikashige, Chihiro Tsutsumi, Yasushi Hiraoka, Hiroshi Kimura, Yasuyuki Ohkawa, Chikashi Obuse, Damien Hermand, Yota Murakami
Some long noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (RNAPII) are retained on chromatin, where they regulate RNAi and chromatin structure. The molecular basis of this retention remains unknown. We show that in fission yeast serine 7 (Ser7) of the C-terminal domain (CTD) of RNAPII is required for efficient siRNA generation for RNAi-dependent heterochromatin formation. Surprisingly, Ser7 facilitates chromatin retention of nascent heterochromatic RNAs (hRNAs). Chromatin retention of hRNAs and siRNA generation requires both Ser7 and an RNA-binding activity of the chromodomain of Chp1, a subunit of the RNA-induced transcriptional silencing (RITS) complex...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29030393/fanconi-anemia-fancd2-and-fanci-proteins-regulate-the-nuclear-dynamics-of-splicing-factors
#8
María Moriel-Carretero, Sara Ovejero, Marie Gérus-Durand, Dimos Vryzas, Angelos Constantinou
Proteins disabled in the cancer-prone disorder Fanconi anemia (FA) ensure the maintenance of chromosomal stability during DNA replication. FA proteins regulate replication dynamics, coordinate replication-coupled repair of interstrand DNA cross-links, and mitigate conflicts between replication and transcription. Here we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key spliceosomal protein of the U2 small nuclear ribonucleoprotein (U2 snRNP). FANCI is in close proximity to SF3B1 in the nucleoplasm of interphase and mitotic cells...
December 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29027900/rna-polymerase-ii-stalling-at-pre-mrna-splice-sites-is-enforced-by-ubiquitination-of-the-catalytic-subunit
#9
Laura Milligan, Camille Sayou, Alex Tuck, Tatsiana Auchynnikava, Jane Ea Reid, Ross Alexander, Flavia de Lima Alves, Robin Allshire, Christos Spanos, Juri Rappsilber, Jean D Beggs, Grzegorz Kudla, David Tollervey
Numerous links exist between co-transcriptional RNA processing and the transcribing RNAPII. In particular, pre-mRNA splicing was reported to be associated with slowed RNAPII elongation. Here, we identify a site of ubiquitination (K1246) in the catalytic subunit of RNAPII close to the DNA entry path. Ubiquitination was increased in the absence of the Bre5-Ubp3 ubiquitin protease complex. Bre5 binds RNA in vivo, with a preference for exon 2 regions of intron-containing pre-mRNAs and poly(A) proximal sites. Ubiquitinated RNAPII showed similar enrichment...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/28967883/3-2-%C3%A3-resolution-structure-of-the-90s-preribosome-before-a1-pre-rrna-cleavage
#10
Jingdong Cheng, Nikola Kellner, Otto Berninghausen, Ed Hurt, Roland Beckmann
The 40S small ribosomal subunit is cotranscriptionally assembled in the nucleolus as part of a large chaperone complex called the 90S preribosome or small-subunit processome. Here, we present the 3.2-Å-resolution structure of the Chaetomium thermophilum 90S preribosome, which allowed us to build atomic structures for 34 assembly factors, including the Mpp10 complex, Bms1, Utp14 and Utp18, and the complete U3 small nucleolar ribonucleoprotein. Moreover, we visualized the U3 RNA heteroduplexes with a 5' external transcribed spacer (5' ETS) and pre-18S RNA, and their stabilization by 90S factors...
November 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28961236/transcriptome-analysis-of-hypoxic-cancer-cells-uncovers-intron-retention-in-eif2b5-as-a-mechanism-to-inhibit-translation
#11
Lauren K Brady, Hejia Wang, Caleb M Radens, Yue Bi, Milan Radovich, Amit Maity, Cristina Ivan, Mircea Ivan, Yoseph Barash, Constantinos Koumenis
Cells adjust to hypoxic stress within the tumor microenvironment by downregulating energy-consuming processes including translation. To delineate mechanisms of cellular adaptation to hypoxia, we performed RNA-Seq of normoxic and hypoxic head and neck cancer cells. These data revealed a significant down regulation of genes known to regulate RNA processing and splicing. Exon-level analyses classified > 1,000 mRNAs as alternatively spliced under hypoxia and uncovered a unique retained intron (RI) in the master regulator of translation initiation, EIF2B5...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28934475/in-vivo-probing-of-nascent-rna-structures-reveals-principles-of-cotranscriptional-folding
#12
Danny Incarnato, Edoardo Morandi, Francesca Anselmi, Lisa M Simon, Giulia Basile, Salvatore Oliviero
Defining the in vivo folding pathway of cellular RNAs is essential to understand how they reach their final native conformation. We here introduce a novel method, named Structural Probing of Elongating Transcripts (SPET-seq), that permits single-base resolution analysis of transcription intermediates' secondary structures on a transcriptome-wide scale, enabling base-resolution analysis of the RNA folding events. Our results suggest that cotranscriptional RNA folding in vivo is a mixture of cooperative folding events, in which local RNA secondary structure elements are formed as they get transcribed, and non-cooperative events, in which 5'-halves of long-range helices get sequestered into transient non-native interactions until their 3' counterparts have been transcribed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28923949/cytosine-deamination-and-base-excision-repair-cause-r-loop-induced-cag-repeat-fragility-and-instability-in-saccharomyces-cerevisiae
#13
Xiaofeng A Su, Catherine H Freudenreich
CAG/CTG repeats are structure-forming repetitive DNA sequences, and expansion beyond a threshold of ∼35 CAG repeats is the cause of several human diseases. Expanded CAG repeats are prone to breakage, and repair of the breaks can cause repeat contractions and expansions. In this study, we found that cotranscriptional R-loops formed at a CAG-70 repeat inserted into a yeast chromosome. R-loops were further elevated upon deletion of yeast RNaseH genes and caused repeat fragility. A significant increase in CAG repeat contractions was also observed, consistent with previous human cell studies...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28730434/cotranscriptional-production-of-chemically-modified-rna-nanoparticles
#14
Maria L Kireeva, Kirill A Afonin, Bruce A Shapiro, Mikhail Kashlev
RNA nanoparticles consisting of multiple RNA strands of different sequences forming various three-dimensional structures emerge as promising carriers of siRNAs, RNA aptamers, and ribozymes. In vitro transcription of a mixture of dsDNA templates encoding all the subunits of the RNA nanoparticle may result in cotranscriptional self-assembly of the nanoparticle. Based on our experience with production of RNA nanorings, RNA nanocubes, and RNA three-way junctions, we propose a strategy for optimization of the cotranscriptional production of chemically modified ribonuclease-resistant RNA nanoparticles...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28721856/repeat-induced-point-mutation-and-other-genome-defense-mechanisms-in-fungi
#15
REVIEW
Eugene Gladyshev
Transposable elements have colonized the genomes of nearly all organisms, including fungi. Although transposable elements may sometimes provide beneficial functions to their hosts their overall impact is considered deleterious. As a result, the activity of transposable elements needs to be counterbalanced by the host genome defenses. In fungi, the primary genome defense mechanisms include repeat-induced point mutation (RIP) and methylation induced premeiotically, meiotic silencing by unpaired DNA, sex-induced silencing, cosuppression (also known as somatic quelling), and cotranscriptional RNA surveillance...
July 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28701519/nineteen-complex-related-factor-prp45-is-required-for-the-early-stages-of-cotranscriptional-spliceosome-assembly
#16
Martina Hálová, Ondřej Gahura, Martin Převorovský, Zdeněk Cit, Marian Novotný, Anna Valentová, Kateřina Abrhámová, František Půta, Petr Folk
Splicing in S. cerevisiae has been shown to proceed cotranscriptionally, but the nature of the coupling remains a subject of debate. Here, we examine the effect of nineteen complex-related splicing factor Prp45 (a homolog of SNW1/SKIP) on cotranscriptional splicing. RNA-sequencing and RT-qPCR showed elevated pre-mRNA levels but only limited reduction of spliced mRNAs in cells expressing C-terminally truncated Prp45, Prp45(1-169). Assays with a series of reporters containing the AMA1 intron with regulatable splicing confirmed decreased splicing efficiency and showed the leakage of unspliced RNAs in prp45 (1-169) cells...
October 2017: RNA
https://www.readbyqxmd.com/read/28698297/disrupted-prenatal-rna-processing-and-myogenesis-in-congenital-myotonic-dystrophy
#17
James D Thomas, Łukasz J Sznajder, Olgert Bardhi, Faaiq N Aslam, Zacharias P Anastasiadis, Marina M Scotti, Ichizo Nishino, Masayuki Nakamori, Eric T Wang, Maurice S Swanson
Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTGexp ) disorder caused by expression of CUGexp RNAs. These mutant RNAs alter the activities of RNA processing factors, including MBNL proteins, leading to re-expression of fetal isoforms in adult tissues and DM1 pathology. While this pathogenesis model accounts for adult-onset disease, the molecular basis of congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of developmentally regulated RNA alternative processing pathways contributes to CDM disease...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28693387/the-flc-locus-a-platform-for-discoveries-in-epigenetics-and-adaptation
#18
Charles Whittaker, Caroline Dean
Our understanding of the detailed molecular mechanisms underpinning adaptation is still poor. One example for which mechanistic understanding of regulation has converged with studies of life history variation is Arabidopsis thaliana FLOWERING LOCUS C (FLC). FLC determines the need for plants to overwinter and their ability to respond to prolonged cold in a process termed vernalization. This review highlights how molecular analysis of vernalization pathways has revealed important insight into antisense-mediated chromatin silencing mechanisms that regulate FLC...
October 6, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28581511/rna-fate-determination-through-cotranscriptional-adenosine-methylation-and-microprocessor-binding
#19
Philip Knuckles, Sarah H Carl, Michael Musheev, Christof Niehrs, Alice Wenger, Marc Bühler
Eukaryotic gene expression is heavily regulated at the transcriptional and post-transcriptional levels. An additional layer of regulation occurs co-transcriptionally through processing and decay of nascent transcripts physically associated with chromatin. This process involves RNA interference (RNAi) machinery and is well documented in yeast, but little is known about its conservation in mammals. Here we show that Dgcr8 and Drosha physically associate with chromatin in murine embryonic stem cells (mES), specifically with a subset of transcribed coding and noncoding genes...
July 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28446598/the-histone-variant-h2a-z-promotes-efficient-cotranscriptional-splicing-in-s-cerevisiae
#20
Lauren T Neves, Stephen Douglass, Roberto Spreafico, Srivats Venkataramanan, Tracy L Kress, Tracy L Johnson
In eukaryotes, a dynamic ribonucleic protein machine known as the spliceosome catalyzes the removal of introns from premessenger RNA (pre-mRNA). Recent studies show the processes of RNA synthesis and RNA processing to be spatio-temporally coordinated, indicating that RNA splicing takes place in the context of chromatin. H2A.Z is a highly conserved histone variant of the canonical histone H2A. In Saccharomyces cerevisiae , H2A.Z is deposited into chromatin by the SWR-C complex, is found near the 5' ends of protein-coding genes, and has been implicated in transcription regulation...
April 1, 2017: Genes & Development
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