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by Thomas Ohrt, Peter Odenwälder, Julia Dannenberg, et al.Mira Prior, Zbigniew Warkocki, Jana Schmitzová, Ramazan Karaduman, Ingo Gregor, Jörg Enderlein, Patrizia Fabrizio, Reinhard Lührmann
posted to mechanism pre-mrna rna splicing yeast
by gonzalez
on 2013-05-24 18:52:32
Abstract
Step 2 catalysis of pre-mRNA splicing entails the excision of the intron and ligation of the 5' and 3' exons. The tasks of the splicing factors Prp16, Slu7, Prp18, and Prp22 in the formation of the step 2 active site of the spliceosome and in exon ligation, and the timing of their recruitment, remain poorly understood. Using a purified yeast in vitro splicing system, we ...
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posted to hnrnpc rna splicing
by ZuzanaC
on 2013-05-24 15:06:43
Abstract
In a patient with a β-thalassemla intermedia, a mutation was identified in the second intron of the human β-globin gene. The U→G mutation is located within the polypyrimidine tract at position −8 upstream of the 3′ splice site. In vivo, this mutation leads to decreased levels of the hemoglobin protein. Because of the location of the mutation and the role of the polypyrimidine tract in the splicing process, we performed in vitro splicing assays on the pre-messenger RNA (premRNA). We found ...
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Abstract
An international, peer-reviewed genome sciences journal featuring outstanding original research that offers novel insights into the biology of all organisms ...
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by Alex K. Shalek, Rahul Satija, Xian Adiconis, et al.Rona S. Gertner, Jellert T. Gaublomme, Raktima Raychowdhury, Schragi Schwartz, Nir Yosef, Christine Malboeuf, Diana Lu, John T. Trombetta, Dave Gennert, Andreas Gnirke, Alon Goren, Nir Hacohen, Joshua Z. Levin, Hongkun Park, Aviv Regev
Abstract
Recent molecular studies have shown that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels and phenotypic output, with important functional consequences. Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs or proteins simultaneously, because genomic profiling methods could not be applied to single cells until very recently. Here we ...
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Abstract
Motivation: Alternative splicing is central for cellular processes and substantially increases transcriptome and proteome diversity. Aberrant splicing events often have pathological consequences and are associated with various diseases and cancer types. The emergence of next-generation RNA sequencing (RNA-seq) provides an exciting new technology to analyse alternative splicing on a large scale. However, algorithms that enable the analysis of alternative splicing from short-read sequencing are not fully established yet and there are still no standard solutions available for a variety of data ...
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by Jeyanthy Eswaran, Anelia Horvath, Sucheta Godbole, et al.Sirigiri D. Reddy, Prakriti Mudvari, Kazufumi Ohshiro, Dinesh Cyanam, Sujit Nair, Suzanne A. W. Fuqua, Kornelia Polyak, Liliana D. Florea, Rakesh Kumar
posted to breast cancer rna-seq splicing
by nailest
on 2013-05-13 16:44:19
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Abstract
Here, we explore the role of splicing in transcription, employing both genome-wide analysis of human ChIP-seq data and experimental manipulation of exon-intron organization in transgenic cell lines. We show that the activating histone modifications H3K4me3 and H3K9ac map specifically to first exon-intron boundaries. This is surprising, because these marks help recruit general transcription factors (GTFs) to promoters. In genes with long first exons, promoter-proximal levels of H3K4me3 and H3K9ac are greatly reduced; consequently, GTFs and RNA polymerase II are low at ...
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Abstract
Exon 3 of the rat α-tropomyosin (Tpm1) gene is repressed in smooth muscle cells, allowing inclusion of the mutually exclusive partner exon 2. Two key types of elements affect repression of exon 3 splicing: binding sites for polypyrimidine tract-binding protein (PTB) and additional negative regulatory elements consisting of clusters of UGC or CUG motifs. Here, we show that the UGC clusters are bound by muscleblind-like proteins (MBNL), which act as repressors of Tpm1 exon 3. We show that the N-terminal region ...
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Abstract
A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields ...
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Abstract
Ultra-deep RNA sequencing has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We develop MATS (multivariate analysis of transcript splicing), a Bayesian statistical framework for flexible hypothesis testing of differential alternative splicing patterns on RNA-Seq data. MATS uses a multivariate uniform prior to model the between-sample correlation in exon splicing patterns, and a Markov chain Monte Carlo (MCMC) method coupled with a simulation-based adaptive sampling procedure to calculate the P-value and false discovery rate (FDR) of differential alternative ...
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Abstract
Co-transcriptional pre-mRNA processing relies on reversible phosphorylation of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II (RNAP II). In this study, we replaced in live cells the endogenous Rpb1 by S2A Rpb1, where the second serines (Ser2) in the CTD heptapeptide repeats were switched to alanines, to prevent phosphorylation. Although slower, S2A RNAP II was able to transcribe. However, it failed to recruit splicing components such as U2AF65 and U2 snRNA to transcription sites, although the ...
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by N. L. Barbosa-Morais, M. Irimia, Q. Pan, et al.H. Y. Xiong, S. Gueroussov, L. J. Lee, V. Slobodeniuc, C. Kutter, S. Watt, R. Colak, T. Kim, C. M. Misquitta-Ali, M. D. Wilson, P. M. Kim, D. T. Odom, B. J. Frey, B. J. Blencowe
Abstract
How species with similar repertoires of protein-coding genes differ so markedly at the phenotypic level is poorly understood. By comparing organ transcriptomes from vertebrate species spanning ~350 million years of evolution, we observed significant differences in alternative splicing complexity between vertebrate lineages, with the highest complexity in primates. Within 6 million years, the splicing profiles of physiologically equivalent organs diverged such that they are more strongly related to the identity of a species than they are to organ type. Most vertebrate ...
Note (first note only)
Barbosa-Morais, Nuno L
Irimia, Manuel
Pan, Qun
Xiong, Hui Y
Gueroussov, Serge
Lee, Leo J
Slobodeniuc, Valentina
Kutter, Claudia
Watt, Stephen
Colak, Recep
Kim, TaeHyung
Misquitta-Ali, Christine M
Wilson, Michael D
Kim, Philip M
Odom, Duncan T
Frey, Brendan J
Blencowe, Benjamin J
eng
Canadian Institutes of Health Research/Canada
Comparative Study
Research Support, Non-U.S. Gov't
New York, N.Y.
2012/12/22 06:00
Science. 2012 Dec 21;338(6114):1587-93. doi: 10.1126/science.1230612.
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Abstract
Alternative pre-mRNA splicing is a central mode of genetic regulation in higher eukaryotes. Variability in splicing patterns is a major source of protein diversity from the genome. In this review, I describe what is currently known of the molecular mechanisms that control changes in splice site choice. I start with the best-characterized systems from the Drosophila sex determination pathway, and then describe the regulators of other systems about whose mechanisms there is some data. How these regulators are combined into complex ...
Note (first note only)
Black, Douglas L
Annu Rev Biochem. 2003;72:291-336. Epub 2003 Feb 27.
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In Mol Cell Biol, Vol. 18 (1998), 2205-17
Abstract
Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) is an example of highly regulated alternative splicing in which exons IIIb and IIIc are utilized in a mutually exclusive manner in different cell types. The importance of this splicing choice is highlighted by studies which indicate that deregulation of the FGF-R2 splicing is associated with progression of prostate cancer. Loss of expression of a IIIb exon-containing isoform of FGF-R2 [FGF-R2 (IIIb)] accompanies the transition of a well-differentiated, androgen-dependent rat prostate cancer ...
Note (first note only)
Carstens, R P
McKeehan, W L
Garcia-Blanco, M A
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1998/04/07
Mol Cell Biol. 1998 Apr;18(4):2205-17.
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Abstract
Alteration of correct splicing patterns by disruption of an exonic splicing enhancer may be a frequent mechanism by which point mutations cause genetic diseases. Spinal muscular atrophy results from the lack of functional survival of motor neuron 1 gene (SMN1), even though all affected individuals carry a nearly identical, normal SMN2 gene. SMN2 is only partially active because a translationally silent, single-nucleotide difference in exon 7 causes exon skipping. Using ESE motif-prediction tools, mutational analysis and in vivo and in vitro ...
Note (first note only)
Cartegni, Luca
Krainer, Adrian R
Nat Genet. 2002 Apr;30(4):377-84. Epub 2002 Mar 4.
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Abstract
Caspase-5 is a caspase-1-like protease with pro-apoptotic and pro-inflammatory activities. Here we have identified a novel exon at the 5'-end of the human caspase-5 gene. This novel exon was present in six alternatively spliced caspase-5 mRNA variants expressed in human peripheral blood mononuclear cells (PBMC) and encoded the previously unknown amino-terminus of caspase-5. The genomic region upstream of this exon contained sequence elements homologous to those of the caspase-11 promoter in the mouse, and transcription of caspase-5 was upregulated by lipopolysaccharide ...
Note (first note only)
Eckhart, Leopold
Kittel, Christian
Gawlas, Sonja
Gruber, Florian
Mildner, Michael
Jilma, Bernd
Tschachler, Erwin
Biochem Biophys Res Commun. 2006 Sep 22;348(2):682-8. Epub 2006 Jul 28.
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In RNA Biol, Vol. 7 (2010), 462-73
Abstract
Alternative splicing is a general mechanism for regulating gene expression that affects the RNA products of more than 90% of human genes. Not surprisingly, alternative splicing is observed among gene products of metazoan immune systems, which have evolved to efficiently recognize pathogens and discriminate between "self" and "non-self", and thus need to be both diverse and flexible. In this review we focus on the specific interface between alternative splicing and autoimmune diseases, which result from a malfunctioning of the immune system ...
Note (first note only)
Evsyukova, Irina
Somarelli, Jason A
Gregory, Simon G
Garcia-Blanco, Mariano A
eng
R01 CA127727/CA/NCI NIH HHS/
R01 CA127727-03/CA/NCI NIH HHS/
R01 NS060925-01/NS/NINDS NIH HHS/
Research Support, N.I.H., Extramural
Review
2010/07/20 06:00
RNA Biol. 2010 Jul-Aug;7(4):462-73. Epub 2010 Jul 1.
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Abstract
Ron, the tyrosine kinase receptor for the Macrophage-stimulating protein, is involved in cell dissociation, motility, and matrix invasion. DeltaRon, a constitutively active isoform that confers increased motility to expressing cells, is generated through the skipping of exon 11. We show that abnormal accumulation of DeltaRon mRNA occurs in breast and colon tumors. Skipping of exon 11 is controlled by a silencer and an enhancer of splicing located in the constitutive exon 12. The strength of the enhancer parallels the relative abundance ...
Note (first note only)
Ghigna, Claudia
Giordano, Silvia
Shen, Haihong
Benvenuto, Federica
Castiglioni, Fabio
Comoglio, Paolo Maria
Green, Michael R
Riva, Silvano
Biamonti, Giuseppe
Mol Cell. 2005 Dec 22;20(6):881-90.
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by S. G. Gregory, S. Schmidt, P. Seth, et al.J. R. Oksenberg, J. Hart, A. Prokop, S. J. Caillier, M. Ban, A. Goris, L. F. Barcellos, R. Lincoln, J. L. McCauley, S. J. Sawcer, D. A. Compston, B. Dubois, S. L. Hauser, M. A. Garcia-Blanco, M. A. Pericak-Vance, J. L. Haines
Abstract
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located ...
Note (first note only)
Gregory, Simon G
Schmidt, Silke
Seth, Puneet
Oksenberg, Jorge R
Hart, John
Prokop, Angela
Caillier, Stacy J
Ban, Maria
Goris, An
Barcellos, Lisa F
Lincoln, Robin
McCauley, Jacob L
Sawcer, Stephen J
Compston, D A S
Dubois, Benedicte
Hauser, Stephen L
Garcia-Blanco, Mariano A
Pericak-Vance, Margaret A
Haines, Jonathan L
Multiple Sclerosis Genetics Group
068545/Z/02/Wellcome Trust/United Kingdom
GM63090/GM/NIGMS NIH HHS/
NS049477/NS/NINDS NIH HHS/
NS26799/NS/NINDS NIH HHS/
NS32830/NS/NINDS NIH HHS/
Nat Genet. 2007 Sep;39(9):1083-91. Epub 2007 Jul 29.
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by P. Hysi, M. Kabesch, M. F. Moffatt, et al.M. Schedel, D. Carr, Y. Zhang, B. Boardman, E. von Mutius, S. K. Weiland, W. Leupold, C. Fritzsch, N. Klopp, A. W. Musk, A. James, G. Nunez, N. Inohara, W. O. Cookson
Abstract
Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the ...
Note (first note only)
Hysi, Pirro
Kabesch, Michael
Moffatt, Miriam F
Schedel, Michaela
Carr, David
Zhang, Youming
Boardman, Brenda
von Mutius, Erika
Weiland, Stephan K
Leupold, Wolfgang
Fritzsch, Christian
Klopp, Norman
Musk, A William
James, Alan
Nunez, Gabriel
Inohara, Naohiro
Cookson, William O C
England
Hum Mol Genet. 2005 Apr 1;14(7):935-41. Epub 2005 Feb 17.
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Abstract
Over the past decade, it has been shown that alternative splicing (AS) is a major mechanism for the enhancement of transcriptome and proteome diversity, particularly in mammals. Splicing can be found in species from bacteria to humans, but its prevalence and characteristics vary considerably. Evolutionary studies are helping to address questions that are fundamental to understanding this important process: how and when did AS evolve? Which AS events are functional? What are the evolutionary forces that shaped, and continue to shape, ...
Note (first note only)
Keren, Hadas
Lev-Maor, Galit
Ast, Gil
England
Nat Rev Genet. 2010 May;11(5):345-55. Epub 2010 Apr 8.
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Abstract
RIP2/RICK/CARDIAK is a member of the receptor interacting protein kinase (RIP) family. RIP2 promotes NF-kappaB activation as well as activation of the MAPKs JNK, ERK1/2 and p38 MAPK, thereby playing an emergent role in the innate immune response and NOD signaling. Moreover, RIP2 has been shown to interact with the CARD of caspase-1 and to induce IL-1beta maturation as well as in the induction of CD95-mediated programmed cell death by enhancing caspase-8 activity. Here, we report the identification and characterization of ...
Note (first note only)
Krieg, Andreas
Le Negrate, Gaelle
Reed, John C
AI-056324/AI/NIAID NIH HHS/
England
Mol Immunol. 2009 Mar;46(6):1163-70. Epub 2009 Jan 3.
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Abstract
Nramp2 is a gene encoding a transmembrane protein that is important in metal transport, in particular iron. Mutations in nramp2 have been shown to be associated with microcytic anemia in mk/mk mice and defective iron transport in Belgrade rats. Nramp2 contains a classical iron responsive element in the 3' untranslated region that confers iron dependent mRNA stabilization. In this report, we describe a splice variant form of human nramp2 that has the carboxyl terminal 18 amino acids substituted with 25 novel ...
Note (first note only)
Lee, P L
Gelbart, T
West, C
Halloran, C
Beutler, E
eng
DK53505/DK/NIDDK NIH HHS/
Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1998/06/27
Blood Cells Mol Dis. 1998 Jun;24(2):199-215.
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Abstract
Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidoglycan, are responsible for increased susceptibility to Crohn's disease (CD). TLRs and their related plant counterparts, the disease-resistance R proteins, undergo alternative splicing as a means of controlling activity. Here we report that regions of NOD2 RNA transcripts that encode the N-terminal and leucine-rich repeat (LRR) domains are alternatively spliced, potentially creating at least eight putative NOD2 variants. The most common variant is a short truncated isoform designated NOD2-short ...
Note (first note only)
Leung, Euphemia
Hong, Jiwon
Fraser, Alan
Krissansen, Geoffrey W
England
Mol Immunol. 2007 Jan;44(4):284-94. Epub 2006 May 3.
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Abstract
Cells can regulate their protein repertoire in response to extracellular stimuli via alternative splicing; however, the mechanisms controlling this process are poorly understood. The CD45 gene undergoes alternative splicing in response to T-cell activation to regulate T-cell function. The ESS1 splicing silencer in CD45 exon 4 confers basal exon skipping in resting T cells through the activity of hnRNP L and confers activation-induced exon skipping in T cells via previously unknown mechanisms. Here we have developed an in vitro splicing assay ...
Note (first note only)
Melton, Alexis A
Jackson, Jason
Wang, Jiarong
Lynch, Kristen W
R01 GM067719/GM/NIGMS NIH HHS/
T32 GM07062/GM/NIGMS NIH HHS/
Mol Cell Biol. 2007 Oct;27(19):6972-84. Epub 2007 Jul 30.
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Abstract
Splicing regulatory proteins often have distinct activities when bound to exons versus introns. However, less clear is whether variables aside from location can influence activity. HnRNP L binds to a motif present in both CD45 variable exons 4 and 5 to affect their coordinate repression. Here, we show that, in contrast to its direct repression of exon 4, hnRNP L represses exon 5 by countering the activity of a neighboring splicing enhancer. In the absence of the enhancer, hnRNP L unexpectedly ...
Note (first note only)
Motta-Mena, Laura B
Heyd, Florian
Lynch, Kristen W
R01 GM067719/GM/NIGMS NIH HHS/
R01 GM067719-07/GM/NIGMS NIH HHS/
R01 GM067719-09/GM/NIGMS NIH HHS/
R01 GM084034-04/GM/NIGMS NIH HHS/
Mol Cell. 2010 Jan 29;37(2):223-34.
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Abstract
The transition from naive to activated T cells is marked by alternative splicing of pre-mRNA encoding the transmembrane phosphatase CD45. Using a short hairpin RNA interference screen, we identified heterogeneous ribonucleoprotein L-like (hnRNPLL) as a critical inducible regulator of CD45 alternative splicing. HnRNPLL was up-regulated in stimulated T cells, bound CD45 transcripts, and was both necessary and sufficient for CD45 alternative splicing. Depletion or overexpression of hnRNPLL in B and T cell lines and primary T cells resulted in reciprocal alteration ...
Note (first note only)
Oberdoerffer, Shalini
Moita, Luis Ferreira
Neems, Daniel
Freitas, Rui P
Hacohen, Nir
Rao, Anjana
AI40127/AI/NIAID NIH HHS/
AI44432/AI/NIAID NIH HHS/
CA42471/CA/NCI NIH HHS/
R01 AI040127-18/AI/NIAID NIH HHS/
R01 AI040127-19/AI/NIAID NIH HHS/
R01 AI044432-09/AI/NIAID NIH HHS/
R01 AI044432-10/AI/NIAID NIH HHS/
R01 AI080875-01/AI/NIAID NIH HHS/
R01 CA042471-23/CA/NCI NIH HHS/
R21 AI071060/AI/NIAID NIH HHS/
R21 AI071060-01/AI/NIAID NIH HHS/
R21 AI071060-02/AI/NIAID NIH HHS/
T32 HL066987/HL/NHLBI NIH HHS/
U19 AI070352/AI/NIAID NIH HHS/
New York, N.Y.
Science. 2008 Aug 1;321(5889):686-91. Epub 2008 Jul 10.
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In Proceedings of the National Academy of Sciences of the United States of America, Vol. 100 (2003), 9440-5, doi:10.1073/pnas.1530509100
Abstract
With the increase in genomewide experiments and the sequencing of multiple genomes, the analysis of large data sets has become commonplace in biology. It is often the case that thousands of features in a genomewide data set are tested against some null hypothesis, where a number of features are expected to be significant. Here we propose an approach to measuring statistical significance in these genomewide studies based on the concept of the false discovery rate. This approach offers a sensible balance ...
Note (first note only)
Storey, John D
Tibshirani, Robert
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5. Epub 2003 Jul 25.
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Abstract
Ribonucleoproteins (RNPs) mediate key cellular functions such as gene expression and its regulation. Whereas most RNP enzymes are stable in composition and harbor preformed active sites, the spliceosome, which removes noncoding introns from precursor messenger RNAs (pre-mRNAs), follows fundamentally different strategies. In order to provide both accuracy to the recognition of reactive splice sites in the pre-mRNA and flexibility to the choice of splice sites during alternative splicing, the spliceosome exhibits exceptional compositional and structural dynamics that are exploited during substrate-dependent ...
Note (first note only)
Wahl, Markus C
Will, Cindy L
Luhrmann, Reinhard
Cell. 2009 Feb 20;136(4):701-18.
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Abstract
One of the earliest steps in metazoan pre-mRNA splicing involves binding of U2 snRNP auxiliary factor (U2AF) 65 KDa subunit to the polypyrimidine (Py) tract and of the 35 KDa subunit to the invariant AG dinucleotide at the intron 3' end. Here we use in vitro and in vivo depletion, as well as reconstitution assays using purified components, to identify hnRNP A1 as an RNA binding protein ...
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Abstract
Ribonucleoproteins (RNPs) mediate key cellular functions such as gene expression and its regulation. Whereas most RNP enzymes are stable in composition and harbor preformed active sites, the spliceosome, which removes noncoding introns from precursor messenger RNAs (pre-mRNAs), follows fundamentally different strategies. In order to provide both accuracy to the recognition of reactive splice sites in the pre-mRNA and flexibility to the choice of splice sites during alternative splicing, the spliceosome exhibits exceptional compositional and structural dynamics that are exploited during substrate-dependent ...
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by Cui-Jun J. Zhang, Jin-Xing X. Zhou, Jun Liu, et al.Ze-Yang Y. Ma, Su-Wei W. Zhang, Kun Dou, Huan-Wei W. Huang, Tao Cai, Renyi Liu, Jian-Kang K. Zhu, Xin-Jian J. He
Abstract
DNA methylation in transposons and other DNA repeats is conserved in plants as well as in animals. In Arabidopsis thaliana, an RNA-directed DNA methylation (RdDM) pathway directs de novo DNA methylation. We performed a forward genetic screen for suppressors of the DNA demethylase mutant ros1 and identified a novel Zinc-finger and OCRE domain-containing Protein 1 (ZOP1) that promotes Pol IV-dependent siRNA accumulation, DNA methylation, and transcriptional silencing. Whole-genome methods disclosed the genome-wide effects of zop1 on Pol IV-dependent siRNA accumulation and ...
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Abstract
Ribosomal proteins are essential to life. While the functions of ribosomal protein-encoding genes (RPGs) are highly conserved, the evolution of their regulatory mechanisms is remarkably dynamic. In Saccharomyces cerevisiae, RPGs are unusual in that they are commonly present as two highly similar gene copies and in that they are over-represented among intron-containing genes. To investigate the role of introns in the regulation of RPG expression, we constructed 16 S. cerevisiae strains with precise deletions of RPG introns. We found that several ...
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posted to splicing
by JeenaRajan ✚
on 2013-04-16 14:39:18
Abstract
A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields ...
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Abstract
Most mammalian pre-mRNAs are alternatively spliced in a manner that alters the resulting open reading frame. Consequently, alternative pre-mRNA splicing provides an important RNA-based layer of protein regulation and cellular function. The ubiquitous nature of alternative splicing coupled with the advent of technologies that allow global interrogation of the transcriptome have led to an increasing awareness of the possibility that widespread changes in splicing patterns ...
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Abstract
Alternative splicing (AS) generates multiple types of mRNA from a single type of pre-mRNA by differential intron splicing. It can result in new protein isoforms or down-regulation of gene expression by transcript decay. The evolutionary conservation of AS events in plants is largely unexplored and only a small number of AS events have been identified as conserved between divergent species. We performed a large-scale analysis ...
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Abstract
Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 52 end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 52-to-32 exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly ...
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Abstract
Precursor mRNA splicing is one of the most highly regulated processes in metazoan species. In addition to generating vast repertoires of RNAs and proteins, splicing has a profound impact on other gene regulatory layers, including mRNA transcription, turnover, transport, and translation. Conversely, factors regulating chromatin and transcription complexes impact the splicing process. This extensive crosstalk between gene regulatory layers takes advantage of dynamic spatial, physical, and temporal organizational properties of the cell nucleus, and further emphasizes the importance of developing a ...
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Abstract
Large portions of the genome undergo alternative pre-mRNA splicing in often intricate patterns. Alternative splicing regulation requires extensive control mechanisms since errors can have deleterious consequences and may lead to developmental defects and disease. Recent work has identified a complex network of regulatory RNA elements which guide splicing decisions. In addition, the discovery that transcription and splicing are intimately coupled has opened up new directions into alternative splicing regulation. Work at the interface of chromatin and RNA biology has revealed unexpected ...
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Abstract
Alternative splicing (AS) is a key regulatory mechanism that contributes to transcriptome and proteome diversity. As very few genome-wide studies analyzing AS in plants are available, we have performed high-throughput sequencing of a normalized cDNA library which resulted in a high coverage transcriptome map of Arabidopsis. We detect ∼150,000 splice junctions derived mostly from typical plant introns, including an eightfold increase in the number of ...
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Abstract
Splicing is one of the major contributors to observed spatiotemporal diversification of transcripts and proteins in metazoans. There are numerous factors that affect the process, but splice sites themselves along with the adjacent splicing signals are critical here. Unfortunately, there is still little known about splicing in plants and, consequently, further research in some fields of plant molecular biology will encounter difficulties. Keeping this in mind, we performed a large-scale analysis of splice sites in eight plant species, using novel algorithms ...
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Abstract
Alternative splicing (AS) is the process by which splice sites in precursor (pre)-mRNA are differentially selected to produce multiple mRNA and protein isoforms. During the past few years the application of genome-wide profiling technologies coupled with bioinformatic approaches has transformed our understanding of AS complexity and regulation. These studies are further driving research directed at elucidating the functions of networks of regulated AS events in the context of normal physiology and disease. Major strides have also been made in understanding how ...
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Abstract
Human genes contain a dense array of diverse cis-acting elements that make up a code required for the expression of correctly spliced mRNAs. Alternative splicing generates a highly dynamic human proteome through networks of coordinated splicing events. Cis- and trans-acting mutations that disrupt the splicing code or the machinery required for splicing and its regulation have roles in various diseases, and recent studies have provided new insights into the mechanisms by which these effects occur. An unexpectedly large fraction of exonic ...
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by Oz Solomon, Shirley Oren, Michal Safran, et al.Naamit Deshet-Unger, Pinchas Akiva, Jasmine Jacob-Hirsch, Karen Cesarkas, Reut Kabesa, Ninette Amariglio, Ron Unger, Gideon Rechavi, Eran Eyal
Abstract
Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of the phenomenon, the regulation and specificity of the splicing machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing of pre-mRNA by ADAR enzymes has been linked to splicing regulation in several cases. Here we used bioinformatics approaches, RNA-seq and exon-specific microarray of ADAR knockdown cells to globally examine how ADAR and its A-to-I RNA editing activity influence alternative mRNA splicing. Although A-to-I RNA editing ...
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posted to introns snorna splicing
by sb71945 ✚
on 2013-03-19 15:40:44
Abstract
The role of spliceosomal intronic structures played in evolution has only begun to be elucidated. Comparative genomic analyses of fungal snoRNA sequences, which are often contained within introns and/or exons, revealed that about one-third of snoRNA-associated introns in three major snoRNA gene clusters manifested polymorphisms, likely resulting from intron loss and gain events during fungi evolution. Genomic deletions can clearly be observed as one mechanism underlying intron and exon loss, as well as generation of complex introns where several introns lie ...
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Abstract
Alternative splicing was discovered simultaneously with splicing over three decades ago. Since then, an enormous body of evidence has demonstrated the prevalence of alternative splicing in multicellular eukaryotes, its key roles in determining tissue- and species-specific differentiation patterns, the multiple post- and co-transcriptional regulatory mechanisms that control it, and its causal role in hereditary disease and cancer. The emerging evidence places alternative splicing in a central position in the flow of eukaryotic genetic information, between transcription and translation, in that it ...
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Abstract
Using the yeast Cryptococcus neoformans, we describe a mechanism by which transposons are initially targeted for RNAi-mediated genome defense. We show that intron-containing mRNA precursors template siRNA synthesis. We identify a Spliceosome-Coupled And Nuclear RNAi (SCANR) complex required for siRNA synthesis and demonstrate that it physically associates with the spliceosome. We find that RNAi target transcripts are distinguished by suboptimal introns and abnormally high occupancy ...
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Abstract
The utilization of stored RNA is a driving force in rapid development. Here, we show that retention and subsequent removal of introns from pre-mRNAs regulate temporal patterns of translation during rapid and posttranscriptionally controlled spermatogenesis of the fern Marsilea vestita. Analysis of RNAseq-derived transcriptomes revealed a large subset of intron-retaining transcripts (IRTs) that encode proteins essential for gamete development. Genomic and IRT sequence comparisons show that other introns have been previously removed from the IRT pre-mRNAs. Fully spliced isoforms appear at distinct ...
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