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Rna splicing

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https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#1
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28430982/evidence-of-nuclei-encoded-spliceosome-mediating-splicing-of-mitochondrial-rna
#2
Roberto H Herai, Priscilla D Negraes, Alysson R Muotri
Mitochondria are thought to have originated as free-living prokaryotes. Mitochondria organelles have small circular genomes with substantial structural (absence of histones and introns) and genetic similarity to bacteria. Contrary to the prevailing concept of intronless mitochondria, here we present evidences that mitochondrial RNA transcripts (mtRNA) are not limited to policystronic molecules, but also processed as nuclei-like transcripts that are differentially spliced and expressed in a cell-type specific manner...
April 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28429321/euglena-transcript-processing
#3
David C McWatters, Anthony G Russell
RNA transcript processing is an important stage in the gene expression pathway of all organisms and is subject to various mechanisms of control that influence the final levels of gene products. RNA processing involves events such as nuclease-mediated cleavage, removal of intervening sequences referred to as introns and modifications to RNA structure (nucleoside modification and editing). In Euglena, RNA transcript processing was initially examined in chloroplasts because of historical interest in the secondary endosymbiotic origin of this organelle in this organism...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28429085/the-role-of-rna-alternative-splicing-in-regulating-cancer-metabolism
#4
REVIEW
Itamar Kozlovski, Zahava Siegfried, Adi Amar-Schwartz, Rotem Karni
Tumor cells alter their metabolism by a wide array of mechanisms to promote growth and proliferation. Dysregulated expression and/or somatic mutations of key components of the glycolytic pathway/TCA cycle as well as other metabolic pathways allow tumor cells to improve their ability to survive harsh conditions such as hypoxia and the presence of reactive oxygen species, as well as the ability to obtain nutrients to increase lipids, protein, and nucleic acids biogenesis. Approximately 95% of the human protein encoding genes undergo alternative splicing (AS), a regulated process of gene expression that greatly diversifies the proteome by creating multiple proteins from a single gene...
April 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#5
Ahn R Lee, Yinan Li, Ning Xie, Martin E Gleave, Michael E Cox, Colin C Collins, Xuesen Dong
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424332/improving-genetic-diagnosis-in-mendelian-disease-with-transcriptome-sequencing
#6
Beryl B Cummings, Jamie L Marshall, Taru Tukiainen, Monkol Lek, Sandra Donkervoort, A Reghan Foley, Veronique Bolduc, Leigh B Waddell, Sarah A Sandaradura, Gina L O'Grady, Elicia Estrella, Hemakumar M Reddy, Fengmei Zhao, Ben Weisburd, Konrad J Karczewski, Anne H O'Donnell-Luria, Daniel Birnbaum, Anna Sarkozy, Ying Hu, Hernan Gonorazky, Kristl Claeys, Himanshu Joshi, Adam Bournazos, Emily C Oates, Roula Ghaoui, Mark R Davis, Nigel G Laing, Ana Topf, Peter B Kang, Alan H Beggs, Kathryn N North, Volker Straub, James J Dowling, Francesco Muntoni, Nigel F Clarke, Sandra T Cooper, Carsten G Bönnemann, Daniel G MacArthur
Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28423643/pole-and-pold1-screening-in-155-patients-with-multiple-polyps-and-early-onset-colorectal-cancer
#7
Clara Esteban-Jurado, David Giménez-Zaragoza, Jenifer Muñoz, Sebastià Franch-Expósito, Miriam Álvarez-Barona, Teresa Ocaña, Miriam Cuatrecasas, Sabela Carballal, María López-Cerón, Maria Marti-Solano, Marcos Díaz-Gay, Tom van Wezel, Antoni Castells, Luis Bujanda, Judith Balmaña, Victoria Gonzalo, Gemma Llort, Clara Ruiz-Ponte, Joaquín Cubiella, Francesc Balaguer, Rosa Aligué, Sergi Castellví-Bel
Germline mutations in POLE and POLD1 have been shown to cause predisposition to colorectal multiple polyposis and a wide range of neoplasms, early-onset colorectal cancer being the most prevalent. In order to find additional mutations affecting the proofreading activity of these polymerases, we sequenced its exonuclease domain in 155 patients with multiple polyps or an early-onset colorectal cancer phenotype without alterations in the known hereditary colorectal cancer genes. Interestingly, none of the previously reported mutations in POLE and POLD1 were found...
March 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423325/rapid-genome-wide-recruitment-of-rna-polymerase-ii-drives-transcription-splicing-and-translation-events-during-t-cell-responses
#8
Kathrin Davari, Johannes Lichti, Christian Gallus, Franziska Greulich, N Henriette Uhlenhaut, Matthias Heinig, Caroline C Friedel, Elke Glasmacher
Activation of immune cells results in rapid functional changes, but how such fast changes are accomplished remains enigmatic. By combining time courses of 4sU-seq, RNA-seq, ribosome profiling (RP), and RNA polymerase II (RNA Pol II) ChIP-seq during T cell activation, we illustrate genome-wide temporal dynamics for ∼10,000 genes. This approach reveals not only immediate-early and posttranscriptionally regulated genes but also coupled changes in transcription and translation for >90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily mediates transcriptional changes...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422315/regulation-of-the-alternative-splicing-and-function-of-cyclin-t1-by-the-serine-arginine-rich-protein-asf-sf2
#9
Jieqiong Zhou, Guozhen Gao, Panpan Hou, Chun-Mei Li, Deyin Guo
Positive transcription elongation factor-b (P-TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for efficient proceeding to the transcription elongation. It consists of two core subunits - CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is the major and most studied combination. We have previously identified a novel splice variant of cyclin T1, cyclin T1b, which negatively regulates the transcription elongation of HIV-1 genes as well as several host genes...
April 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28420616/aberrant-rna-splicing-as-the-molecular-basis-of-some-pathogenic-variants
#10
Zou Yongxin, Gong Yaoqin
Identification and correct classification of disease-associated mutations are essential for molecular diagnosis and clinical management of many genetic disorders. Although next-generation sequencing has greatly accelerated the detection of nucleotide changes, the biological interpretation of most variants has become a real challenge. Moreover, attention is typically paid to protein-coding changes and the potential impact of exonic variants on RNA splicing is often ignored. There is increasing evidence showing that disease-causing aberrant RNA splicing is more widespread than currently appreciated...
March 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28419381/enhancing-faba-bean-vicia-faba-l-genome-resources
#11
James W Cooper, Michael H Wilson, Martijn F L Derks, Sandra Smit, Karl J Kunert, Christopher Cullis, Christine H Foyer
Grain legume improvement is currently impeded by a lack of genomic resources. The paucity of genome information for faba bean can be attributed to the intrinsic difficulties of assembling/annotating its giant (~13 Gb) genome. In order to address this challenge, RNA-sequencing analysis was performed on faba bean (cv. Wizard) leaves. Read alignment to the faba bean reference transcriptome identified 16 300 high quality unigenes. In addition, Illumina paired-end sequencing was used to establish a baseline for genomic information assembly...
April 17, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28418914/met-exon-14-mutations-as-targets-in-routine-molecular-analysis-of-primary-sarcomatoid-carcinoma-of-the-lung
#12
Raphaël Saffroy, Vincent Fallet, Nicolas Girard, Julien Mazieres, Denis Moro Sibilot, Sylvie Lantuejoul, Isabelle Rouquette, Françoise Thivolet-Bejui, Thibaut Vieira, Martine Antoine, Jacques Cadranel, Antoinette Lemoine, Marie Wislez
MET exon 14 splicing mutations are new targetable oncogenic drivers reported in 3% of non-small cell lung cancer (NSCLC) cases and have been shown to be more common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian patients, with a large adenocarcinoma cohort as internal control.We tested 81 patients with SC and 150 with adenocarcinoma for splice site DNA mutations leading to RNA splicing-based skipping of MET exon 14...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418892/roles-of-long-noncoding-rnas-in-colorectal-cancer-metastasis
#13
REVIEW
He Li, Si-Qing Ma, Jin Huang, Xiao-Ping Chen, Hong-Hao Zhou
Colorectal cancer (CRC) is the 3rd most common malignancies worldwide. Metastasis is responsible for more than 90% CRC patients' death. Long noncoding RNAs (lncRNAs) are an important class of transcribed RNA molecules greater than 200 nucleotides in length. With the development of whole genome sequencing technologies, they have been gained more attention. Accumulating evidences suggest that abnormal expression of lncRNAs in diverse diseases are involved in various biological functions such as proliferation, apoptosis, metastasis and differentiation by acting as epigenetic, splicing, transcriptional or post-transcriptional regulators...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418376/a-circrna-from-sepallata3-regulates-splicing-of-its-cognate-mrna-through-r-loop-formation
#14
Vanessa M Conn, Véronique Hugouvieux, Aditya Nayak, Stephanie A Conos, Giovanna Capovilla, Gökhan Cildir, Agnès Jourdain, Vinay Tergaonkar, Markus Schmid, Chloe Zubieta, Simon J Conn
Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life(1), yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family...
April 18, 2017: Nature Plants
https://www.readbyqxmd.com/read/28416802/rna-editing-dependent-epitranscriptome-diversity-in-cancer-stem-cells
#15
REVIEW
Qingfei Jiang, Leslie A Crews, Frida Holm, Catriona H M Jamieson
Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli...
April 18, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28416714/jinglebells-a-repository-of-immune-related-single-cell-rna-sequencing-datasets
#16
Hadas Ner-Gaon, Ariel Melchior, Nili Golan, Yael Ben-Haim, Tal Shay
Recent advances in single-cell RNA-sequencing (scRNA-seq) technology increase the understanding of immune differentiation and activation processes, as well as the heterogeneity of immune cell types. Although the number of available immune-related scRNA-seq datasets increases rapidly, their large size and various formats render them hard for the wider immunology community to use, and read-level data are practically inaccessible to the non-computational immunologist. To facilitate datasets reuse, we created the JingleBells repository for immune-related scRNA-seq datasets ready for analysis and visualization of reads at the single-cell level (http://jinglebells...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416566/structure-of-deah-rha-atpase-prp43p-bound-to-rna-implicates-a-pair-of-hairpins-and-motif-va-in-translocation-along-rna
#17
Yangzi He, Jonathan P Staley, Gregers Rom Andersen, Klaus H Nielsen
Three families of nucleic acid-dependent ATPases (DEAH/RHA, Ski2-like and NS3/NPH-II), termed the DExH ATPases, are thought to execute myriad functions by processive, ATP-dependent, 3' to 5' translocation along single-stranded nucleic acid. While the mechanism of translocation of the viral NS3/NPH-II family has been studied extensively, it has not been clear if or how the principles that have emerged for this family extend to the other two families. Here we report the crystal structure of the yeast DEAH/RHA family ATPase Prp43p, which functions in splicing and ribosome biogenesis, in complex with poly-uracil and a non-hydrolysable ATP analogue...
April 17, 2017: RNA
https://www.readbyqxmd.com/read/28415823/recurrent-fusion-rna-dus4l-bcap29-in-non-cancer-human-tissues-and-cells
#18
Yue Tang, Fujun Qin, Aiqun Liu, Hui Li
Traditional gene fusions are involved in the development of various neoplasia. DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-fusion in prostate and gastric cancer, in addition to playing a tumorigenic role. Here, we showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal tissues. It is also present in non-cancer epithelial, as well as in fibroblast cell lines. Quantitatively, the fusion transcript has a comparable expression in non-cancerous, gastric and prostate cell lines and tissues as in the cancer cell lines and tissues...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408981/rna-and-proteins-mutual-respect
#19
REVIEW
Kathleen B Hall
Proteins and RNA are often found in ribonucleoprotein particles (RNPs), where they function in cellular processes to synthesize proteins (the ribosome), chemically modify RNAs (small nucleolar RNPs), splice pre-mRNAs (the spliceosome), and, on a larger scale, sequester RNAs, degrade them, or process them (P bodies, Cajal bodies, and nucleoli). Each RNA-protein interaction is a story in itself, as both molecules can change conformation, compete for binding sites, and regulate cellular functions. Recent studies of Xist long non-coding RNP, the U4/5/6 tri-small nuclear RNP complex, and an activated state of a spliceosome reveal new features of RNA interactions with proteins, and, although their stories are incomplete, they are already fascinating...
2017: F1000Research
https://www.readbyqxmd.com/read/28407323/proteogenomic-analysis-reveals-alternative-splicing-and-translation-as-part-of-the-abscisic-acid-response-in-arabidopsis-seedlings
#20
Fu-Yuan Zhu, Mo-Xian Chen, Neng-Hui Ye, Lu Shi, Kai-Long Ma, Jing-Fang Yang, Yun-Ying Cao, Youjun Zhang, Takuya Yoshida, Alisdair R Fernie, Guang-Yi Fan, Bo Wen, Ruo Zhou, Tie-Yuan Liu, Tao Fan, Bei Gao, Di Zhang, Ge-Fei Hao, Shi Xiao, Ying-Gao Liu, Jianhua Zhang
In eukaryotes, mechanisms such as alternative splicing (AS) and alternative translation initiation (ATI) contribute to organismal protein diversity. Specifically, splicing factors play crucial roles in responses to environment and development cues. However, the underlying mechanisms are not well investigated in plants. Here, we report the parallel employment of short-read RNA sequencing, single molecule long-read sequencing and proteomic identification to unravel AS isoforms and previously unannotated proteins in response to abscisic acid (ABA) treatment...
April 13, 2017: Plant Journal: for Cell and Molecular Biology
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