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https://www.readbyqxmd.com/read/28148777/sabotaging-of-the-oxidative-stress-response-by-an-oncogenic-noncoding-rna
#1
Nitin Mahajan, Hua-Jun Wu, Richard L Bennett, Catalina Troche, Jonathan D Licht, Jason D Weber, Leonard B Maggi, Michael H Tomasson
Overexpression of the multiple myeloma set domain (MMSET) Wolf-Hirschhorn syndrome candidate 1 gene, which contains an orphan box H/ACA class small nucleolar RNA, ACA11, in an intron, is associated with several cancer types, including multiple myeloma (MM). ACA11 and MMSET are overexpressed cotranscriptionally as a result of the t(4;14) chromosomal translocation in a subset of patients with MM. RNA sequencing of CD138(+) tumor cells from t(4;14)-positive and -negative MM patient bone marrow samples revealed an enhanced oxidative phosphorylation mRNA signature...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28071751/transcriptional-pausing-at-the-translation-start-site-operates-as-a-critical-checkpoint-for-riboswitch-regulation
#2
Adrien Chauvier, Frédéric Picard-Jean, Jean-Christophe Berger-Dancause, Laurène Bastet, Mohammad Reza Naghdi, Audrey Dubé, Pierre Turcotte, Jonathan Perreault, Daniel A Lafontaine
On the basis of nascent transcript sequencing, it has been postulated but never demonstrated that transcriptional pausing at translation start sites is important for gene regulation. Here we show that the Escherichia coli thiamin pyrophosphate (TPP) thiC riboswitch contains a regulatory pause site in the translation initiation region that acts as a checkpoint for thiC expression. By biochemically probing nascent transcription complexes halted at defined positions, we find a narrow transcriptional window for metabolite binding, in which the downstream boundary is delimited by the checkpoint...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28031484/identification-of-nad-capped-mrnas-in-saccharomyces-cerevisiae
#3
Robert W Walters, Tyler Matheny, Laura S Mizoue, Bhalchandra S Rao, Denise Muhlrad, Roy Parker
RNAs besides tRNA and rRNA contain chemical modifications, including the recently described 5' nicotinamide-adenine dinucleotide (NAD(+)) RNA in bacteria. Whether 5' NAD-RNA exists in eukaryotes remains unknown. We demonstrate that 5' NAD-RNA is found on subsets of nuclear and mitochondrial encoded mRNAs in Saccharomyces cerevisiae NAD-mRNA appears to be produced cotranscriptionally because NAD-RNA is also found on pre-mRNAs, and only on mitochondrial transcripts that are not 5' end processed. These results define an additional 5' RNA cap structure in eukaryotes and raise the possibility that this 5' NAD(+) cap could modulate RNA stability and translation on specific subclasses of mRNAs...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27999816/evidence-for-altered-canonical-wnt-signaling-in-the-trabecular-bone-of-elderly-postmenopausal-women-with-fragility-femoral-fracture
#4
Simona Bolamperti, Isabella Villa, Alice Spinello, Greta Manfredini, Emanuela Mrak, Umberto Mezzadri, Marco Ometti, Gianfranco Fraschini, Francesca Guidobono, Alessandro Rubinacci
Wnt signaling, a major regulator of bone formation and homeostasis, might be involved in the bone loss of osteoporotic patients and the consequent impaired response to fracture. Therefore we analyzed Wnt-related, osteogenic, and adipogenic genes in bone tissue of elderly postmenopausal women undergoing hip replacement for either femoral fracture or osteoarthritis. Bone specimens derived from the intertrochanteric region of the femurs of 25 women with fracture (F) and 29 with osteoarthritis without fracture (OA) were analyzed...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27965595/cutting-a-long-intron-short-recursive-splicing-and-its-implications
#5
Theodore Georgomanolis, Konstantinos Sofiadis, Argyris Papantonis
Over time eukaryotic genomes have evolved to host genes carrying multiple exons separated by increasingly larger intronic, mostly non-protein-coding, sequences. Initially, little attention was paid to these intronic sequences, as they were considered not to contain regulatory information. However, advances in molecular biology, sequencing, and computational tools uncovered that numerous segments within these genomic elements do contribute to the regulation of gene expression. Introns are differentially removed in a cell type-specific manner to produce a range of alternatively-spliced transcripts, and many span tens to hundreds of kilobases...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27927177/initiator-trna-genes-template-the-3-cca-end-at-high-frequencies-in-bacteria
#6
David H Ardell, Ya-Ming Hou
BACKGROUND: While the CCA sequence at the mature 3' end of tRNAs is conserved and critical for translational function, a genetic template for this sequence is not always contained in tRNA genes. In eukaryotes and Archaea, the CCA ends of tRNAs are synthesized post-transcriptionally by CCA-adding enzymes. In Bacteria, tRNA genes template CCA sporadically. RESULTS: In order to understand the variation in how prokaryotic tRNA genes template CCA, we re-annotated tRNA genes in tRNAdb-CE database version 0...
December 8, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27856616/antisense-transcription-licenses-nascent-transcripts-to-mediate-transcriptional-gene-silencing
#7
Yunkun Dang, Jiasen Cheng, Xianyun Sun, Zhipeng Zhou, Yi Liu
In eukaryotes, antisense transcription can regulate sense transcription by induction of epigenetic modifications. We showed previously that antisense transcription triggers Dicer-independent siRNA (disiRNA) production and disiRNA locus DNA methylation (DLDM) in Neurospora crassa Here we show that the conserved exonuclease ERI-1 (enhanced RNAi-1) is a critical component in this process. Antisense transcription and ERI-1 binding to target RNAs are necessary and sufficient to trigger DLDM. Convergent transcription causes stalling of RNA polymerase II during transcription, which permits ERI-1 to bind nascent RNAs in the nucleus and recruit a histone methyltransferase complex that catalyzes chromatin modifications...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27798597/cotranscriptional-folding-of-a-riboswitch-at-nucleotide-resolution
#8
Kyle E Watters, Eric J Strobel, Angela M Yu, John T Lis, Julius B Lucks
RNAs can begin to fold immediately as they emerge from RNA polymerase. During cotranscriptional folding, interactions between nascent RNAs and ligands are able to direct the formation of alternative RNA structures, a feature exploited by noncoding RNAs called riboswitches to make gene-regulatory decisions. Despite their importance, cotranscriptional folding pathways have yet to be uncovered with sufficient resolution to reveal how cotranscriptional folding governs RNA structure and function. To access cotranscriptional folding at nucleotide resolution, we extended selective 2'-hydroxyl acylation analyzed by primer-extension sequencing (SHAPE-seq) to measure structural information of nascent RNAs during transcription...
December 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27779655/human-telomerase-reverse-transcriptase-regulation-by-dna-methylation-transcription-factor-binding-and-alternative-splicing-review
#9
Brittany A Avin, Christopher B Umbricht, Martha A Zeiger
The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), plays an essential role in telomere maintenance to oppose cellular senescence and, is highly regulated in normal and cancerous cells. Regulation of hTERT occurs through multiple avenues, including a unique pattern of CpG promoter methylation and alternative splicing. Promoter methylation affects the binding of transcription factors, resulting in changes in expression of the gene. In addition to expression level changes, changes in promoter binding can affect alternative splicing in a cotranscriptional manner...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27605205/the-pol-ii-ctd-new-twists-in-the-tail
#10
REVIEW
Justyna Zaborowska, Sylvain Egloff, Shona Murphy
The C-terminal domain (CTD) of the large subunit of RNA polymerase (pol) II comprises conserved heptad repeats, and post-translational modification of the CTD regulates transcription and cotranscriptional RNA processing. Recently, the spatial patterns of modification of the CTD repeats have been investigated, and new functions of CTD modification have been revealed. In addition, there are new insights into the roles of the enzymes that decorate the CTD. We review these new findings and reassess the role of the pol II CTD in the regulation of gene expression...
September 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27601672/structural-mechanism-for-the-recognition-and-ubiquitination-of-a-single-nucleosome-residue-by-rad6-bre1
#11
Laura D Gallego, Medini Ghodgaonkar Steger, Anton A Polyansky, Tobias Schubert, Bojan Zagrovic, Ning Zheng, Tim Clausen, Franz Herzog, Alwin Köhler
Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6-Bre1 machinery is unknown. Using chemical cross-linking and mass spectrometry, we identified the functional interfaces of Rad6, Bre1, and NCPs in a defined in vitro system. The Bre1 RING domain cross-links exclusively with distinct regions of histone H2B and H2A, indicating a spatial alignment of Bre1 with the NCP acidic patch...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27582463/rna-binding-protein-dus16-plays-an-essential-role-in-primary-mirna-processing-in-the-unicellular-alga-chlamydomonas-reinhardtii
#12
Tomohito Yamasaki, Masayuki Onishi, Eun-Jeong Kim, Heriberto Cerutti, Takeshi Ohama
Canonical microRNAs (miRNAs) are embedded in duplexed stem-loops in long precursor transcripts and are excised by sequential cleavage by DICER nuclease(s). In this miRNA biogenesis pathway, dsRNA-binding proteins play important roles in animals and plants by assisting DICER. However, these RNA-binding proteins are poorly characterized in unicellular organisms. Here we report that a unique RNA-binding protein, Dull slicer-16 (DUS16), plays an essential role in processing of primary-miRNA (pri-miRNA) transcripts in the unicellular green alga Chlamydomonas reinhardtii In animals and plants, dsRNA-binding proteins involved in miRNA biogenesis harbor two or three dsRNA-binding domains (dsRBDs), whereas DUS16 contains one dsRBD and also an ssRNA-binding domain (RRM)...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27518568/snapshot-transcription-elongation
#13
Christine E Cucinotta, Karen M Arndt
Transcription elongation is a key regulatory step in gene expression that is controlled by many proteins, and mechanisms, ranging from RNA Polymerase II pausing to cotranscriptional histone modifications.
August 11, 2016: Cell
https://www.readbyqxmd.com/read/27465259/the-nuts-and-bolts-of-the-endogenous-spliceosome
#14
REVIEW
Ruth Sperling
The complex life of pre-mRNA from transcription to the production of mRNA that can be exported from the nucleus to the cytoplasm to encode for proteins entails intricate coordination and regulation of a network of processing events. Coordination is required between transcription and splicing and between several processing events including 5' and 3' end processing, splicing, alternative splicing and editing that are major contributors to the diversity of the human proteome, and occur within a huge and dynamic macromolecular machine-the endogenous spliceosome...
January 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27450756/circular-rnas-and-systemic-lupus-erythematosus
#15
REVIEW
Lian-Ju Li, Qing Huang, Hai-Feng Pan, Dong-Qing Ye
Circular RNAs (circRNAs) are a large class of noncoding RNAs that form covalently closed RNA circles. The discovery of circRNAs discloses a new layer of gene regulation occurred post-transcriptionally. Identification of endogenous circRNAs benefits from the advance in high-throughput RNA sequencing and remains challenging. Many studies probing into the mechanisms of circRNAs formation occurred cotranscriptionally or posttranscriptionally emerge and conclude that canonical splicing mechanism, sequence properties, and certain regulatory factors are at play in the process...
August 15, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27401558/the-nrd1-like-protein-seb1-coordinates-cotranscriptional-3-end-processing-and-polyadenylation-site-selection
#16
Jean-François Lemay, Samuel Marguerat, Marc Larochelle, Xiaochuan Liu, Rob van Nues, Judit Hunyadkürti, Mainul Hoque, Bin Tian, Sander Granneman, Jürg Bähler, François Bachand
Termination of RNA polymerase II (RNAPII) transcription is associated with RNA 3' end formation. For coding genes, termination is initiated by the cleavage/polyadenylation machinery. In contrast, a majority of noncoding transcription events in Saccharomyces cerevisiae does not rely on RNA cleavage for termination but instead terminates via a pathway that requires the Nrd1-Nab3-Sen1 (NNS) complex. Here we show that the Schizosaccharomyces pombe ortholog of Nrd1, Seb1, does not function in NNS-like termination but promotes polyadenylation site selection of coding and noncoding genes...
July 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27247267/phosphatase-rtr1-regulates-global-levels-of-serine-5-rna-polymerase-ii-c-terminal-domain-phosphorylation-and-cotranscriptional-histone-methylation
#17
Gerald O Hunter, Melanie J Fox, Whitney R Smith-Kinnaman, Madelaine Gogol, Brian Fleharty, Amber L Mosley
In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3)...
September 1, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27198613/lights-camera-action-capturing-the-spliceosome-and-pre-mrna-splicing-with-single-molecule-fluorescence-microscopy
#18
REVIEW
Alexander C DeHaven, Ian S Norden, Aaron A Hoskins
The process of removing intronic sequences from a precursor to messenger RNA (pre-mRNA) to yield a mature mRNA transcript via splicing is an integral step in eukaryotic gene expression. Splicing is carried out by a cellular nanomachine called the spliceosome that is composed of RNA components and dozens of proteins. Despite decades of study, many fundamentals of spliceosome function have remained elusive. Recent developments in single-molecule fluorescence microscopy have afforded new tools to better probe the spliceosome and the complex, dynamic process of splicing by direct observation of single molecules...
September 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27196733/molybdate-uptake-by-agrobacterium-tumefaciens-correlates-with-the-cellular-molybdenum-cofactor-status
#19
Marie-Christine Hoffmann, Koral Ali, Marleen Sonnenschein, Laura Robrahn, Daria Strauss, Franz Narberhaus, Bernd Masepohl
Many enzymes require the molybdenum cofactor, Moco. Under Mo-limiting conditions, the high-affinity ABC transporter ModABC permits molybdate uptake and Moco biosynthesis in bacteria. Under Mo-replete conditions, Escherichia coli represses modABC transcription by the one-component regulator, ModE, consisting of a DNA-binding and a molybdate-sensing domain. Instead of a full-length ModE protein, many bacteria have a shorter ModE protein, ModE(S) , consisting of a DNA-binding domain only. Here, we asked how such proteins sense the intracellular molybdenum status...
September 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27036125/disruption-of-ribosome-assembly-in-yeast-blocks-cotranscriptional-pre-rrna-processing-and-affects-the-global-hierarchy-of-ribosome-biogenesis
#20
Jason Talkish, Stephanie Biedka, Jelena Jakovljevic, Jingyu Zhang, Lan Tang, John R Strahler, Philip C Andrews, Janine R Maddock, John L Woolford
In higher eukaryotes, pre-rRNA processing occurs almost exclusively post-transcriptionally. This is not the case in rapidly dividing yeast, as the majority of nascent pre-rRNAs are processed cotranscriptionally, with cleavage at the A2 site first releasing a pre-40S ribosomal subunit followed by release of a pre-60S ribosomal subunit upon transcription termination. Ribosome assembly is driven in part by hierarchical association of assembly factors and r-proteins. Groups of proteins are thought to associate with pre-ribosomes cotranscriptionally during early assembly steps, whereas others associate later, after transcription is completed...
June 2016: RNA
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