Genomes and Genes
Summary: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.
- Hahn D, Kudla G, Tollervey D, Beggs J. Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning. Genes Dev. 2012;26:2408-21 pubmed publisher..We propose a previously unsuspected function for Brr2p in driving conformational rearrangements that lead to competence for the second step of splicing. ..
- Je E, Yoo N, Kim Y, Kim M, Lee S. Mutational analysis of splicing machinery genes SF3B1, U2AF1 and SRSF2 in myelodysplasia and other common tumors. Int J Cancer. 2013;133:260-5 pubmed publisher..The data suggest that the splicing gene mutations play important roles in the pathogenesis of hematologic tumors, but rarely in solid tumors. ..
- Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H, Li H, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell. 2013;152:82-96 pubmed publisher..This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage. ..
- van der Burgt A, Severing E, de Wit P, Collemare J. Birth of new spliceosomal introns in fungi by multiplication of introner-like elements. Curr Biol. 2012;22:1260-5 pubmed publisher..We suggest that ILEs not only account for intron gains in six fungi but also in ancestral eukaryotes to give rise to most RSIs by a yet unknown multiplication mechanism...
- Chettouh H, Fartoux L, Aoudjehane L, Wendum D, Clapéron A, Chretien Y, et al. Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. Cancer Res. 2013;73:3974-86 pubmed publisher..Increased expression of IR-A during neoplastic transformation of hepatocytes could mediate some of the adverse effects of hyperinsulinemia on HCC. ..
- Kock J, Rösler C, Zhang J, Blum H, Nassal M, Thoma C. Human hepatitis B virus production in avian cells is characterized by enhanced RNA splicing and the presence of capsids containing shortened genomes. PLoS ONE. 2012;7:e37248 pubmed publisher..Hence, two effects reflecting capsid disassembly in the nucleus in human HepG2 cells are seen in the cytoplasm of chicken LMH cells. ..
- Davidson L, Kerr A, West S. Co-transcriptional degradation of aberrant pre-mRNA by Xrn2. EMBO J. 2012;31:2566-78 pubmed publisher..Our data therefore establish a previously unknown function for Xrn2 and an important further aspect of pre-mRNA metabolism that occurs co-transcriptionally. ..
- Zmudjak M, Colas des Francs Small C, Keren I, Shaya F, Belausov E, Small I, et al. mCSF1, a nucleus-encoded CRM protein required for the processing of many mitochondrial introns, is involved in the biogenesis of respiratory complexes I and IV in Arabidopsis. New Phytol. 2013;199:379-94 pubmed publisher..Analogously to the functions of plastid-localized CRM proteins, analysis of the RNA profiles in wildtype and mcsf1 plants showed that mCSF1 acts in the splicing of many of the group II intron RNAs in Arabidopsis mitochondria. ..
- Ajiro M, Jia R, Zhang L, Liu X, Zheng Z. Intron definition and a branch site adenosine at nt 385 control RNA splicing of HPV16 E6*I and E7 expression. PLoS ONE. 2012;7:e46412 pubmed publisher..selected over the other splice sites crossing over the intron to excise a minimal length of the intron in RNA splicing. We identified AACAAAC as the preferred branch point sequence (BPS) and an adenosine at nt 385 (underlined) in ..
- Steckelberg A, Boehm V, Gromadzka A, Gehring N. CWC22 connects pre-mRNA splicing and exon junction complex assembly. Cell Rep. 2012;2:454-61 pubmed publisher..Our work establishes a direct link between the splicing machinery and the EJC, hence uncovering a molecular interaction at the center of a posttranscriptional gene regulation network. ..
- Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15-21 pubmed publisher..STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/. ..
- Purcell J, Oddo J, Wang E, Berglund J. Combinatorial mutagenesis of MBNL1 zinc fingers elucidates distinct classes of regulatory events. Mol Cell Biol. 2012;32:4155-67 pubmed..We demonstrate that functionally distinct classes of MBNL1-mediated splicing events exist as defined by requirements for ZF-RNA interactions. ..
- Khrouchtchova A, Monde R, Barkan A. A short PPR protein required for the splicing of specific group II introns in angiosperm chloroplasts. RNA. 2012;18:1197-209 pubmed publisher..THA8 is the first member of this subfamily with a defined molecular function, and illustrates that even small PPR proteins have the potential to mediate specific intermolecular interactions in vivo. ..
- Sahashi K, Hua Y, Ling K, Hung G, Rigo F, Horev G, et al. TSUNAMI: an antisense method to phenocopy splicing-associated diseases in animals. Genes Dev. 2012;26:1874-84 pubmed publisher..This approach allows the dissection of pathogenesis mechanisms, including spatial and temporal features of disease onset and progression, as well as testing of candidate therapeutics. ..
- McCloskey A, Taniguchi I, Shinmyozu K, Ohno M. hnRNP C tetramer measures RNA length to classify RNA polymerase II transcripts for export. Science. 2012;335:1643-6 pubmed publisher..Our findings reveal a new function of the C tetramer and highlight the biological importance of RNA recognition by the length. ..
- Hoskins A, Moore M. The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem Sci. 2012;37:179-88 pubmed publisher..These experiments are rewriting the textbooks, with a new picture emerging of a dynamic, malleable machine heavily influenced by the identity of its pre-mRNA substrate. ..
- Acedo A, Sanz D, Duran M, Infante M, Perez Cabornero L, Miner C, et al. Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes. Breast Cancer Res. 2012;14:R87 pubmed..The minigene system is a straightforward and robust approach to detect variants with an impact on splicing and contributes to a better knowledge of this gene expression step. ..
- Moss W, Dela Moss L, Kierzek E, Kierzek R, Priore S, Turner D. The 3' splice site of influenza A segment 7 mRNA can exist in two conformations: a pseudoknot and a hairpin. PLoS ONE. 2012;7:e38323 pubmed publisher..The results suggest that segment 7 mRNA splicing can be controlled by a conformational switch that exposes or hides the splice site. ..
- Fedorova O, Pyle A. The brace for a growing scaffold: Mss116 protein promotes RNA folding by stabilizing an early assembly intermediate. J Mol Biol. 2012;422:347-65 pubmed publisher..In addition, the data reveal an important role for the IBS2 exon sequence and for the terminus of domain 6, during the folding of self-splicing group IIB intron constructs. ..
- Singh G, Kucukural A, Cenik C, Leszyk J, Shaffer S, Weng Z, et al. The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus. Cell. 2012;151:750-764 pubmed publisher..Further, their protection of long mRNA stretches from nuclease digestion suggests that endogenous EJCs and SR proteins cooperate to promote mRNA packaging and compaction. ..
- Shankarling G, Lynch K. Minimal functional domains of paralogues hnRNP L and hnRNP LL exhibit mechanistic differences in exonic splicing repression. Biochem J. 2013;453:271-9 pubmed publisher..Thus the results of the present study provide important insight into the functional and mechanistic variations that can exist between two highly related hnRNP proteins. ..
- Childs Disney J, Parkesh R, Nakamori M, Thornton C, Disney M. Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1. ACS Chem Biol. 2012;7:1984-93 pubmed publisherMyotonic dystrophy type 1 (DM1) is caused when an expanded r(CUG) repeat (r(CUG)(exp)) binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1) as well as other proteins...
- Avendaño Vázquez S, Dhir A, Bembich S, Buratti E, Proudfoot N, Baralle F. Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection. Genes Dev. 2012;26:1679-84 pubmed publisher..Overall, we uncover complex interplay between transcription, splicing, and 3' end processing to effect autoregulation of TDP-43. ..
- Pandit S, Zhou Y, Shiue L, Coutinho Mansfield G, Li H, Qiu J, et al. Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing. Mol Cell. 2013;50:223-35 pubmed publisher..Therefore, specific effects on regulated splicing by one SR protein actually depend on a complex set of relationships with multiple other SR proteins in mammalian genomes. ..
- Chazal P, Daguenet E, Wendling C, Ulryck N, Tomasetto C, Sargueil B, et al. EJC core component MLN51 interacts with eIF3 and activates translation. Proc Natl Acad Sci U S A. 2013;110:5903-8 pubmed publisher..Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery. ..
- Windhager L, Bonfert T, Burger K, Ruzsics Z, Krebs S, Kaufmann S, et al. Ultrashort and progressive 4sU-tagging reveals key characteristics of RNA processing at nucleotide resolution. Genome Res. 2012;22:2031-42 pubmed publisher..In summary, our study yields unparalleled insights into the kinetics of RNA processing and provides the tools to study molecular mechanisms of RNA processing and their contribution to the regulation of gene expression. ..
- van Roon Mom W, Aartsma Rus A. Overview on applications of antisense-mediated exon skipping. Methods Mol Biol. 2012;867:79-96 pubmed publisher..For each application, examples are discussed and the current state of the art is described. ..
- Chiou N, Shankarling G, Lynch K. hnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. Mol Cell. 2013;49:972-82 pubmed publisher..Together, our results demonstrate that conformational perturbations within the spliceosome are a naturally occurring and generalizable mechanism for controlling alternative splicing decisions...
- Arnold E, Ling S, Huelga S, Lagier Tourenne C, Polymenidou M, Ditsworth D, et al. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci U S A. 2013;110:E736-45 pubmed publisher..Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage. ..
- Berson A, Barbash S, Shaltiel G, Goll Y, Hanin G, Greenberg D, et al. Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice. EMBO Mol Med. 2012;4:730-42 pubmed publisher..Our findings present cholinergic-mediated hnRNP A/B loss and impaired RNA metabolism as important mechanisms involved in AD. ..
- Ilagan J, Chalkley R, Burlingame A, Jurica M. Rearrangements within human spliceosomes captured after exon ligation. RNA. 2013;19:400-12 pubmed publisher..Our ability to compare human spliceosomes before and after second-step chemistry has opened a new window to rearrangements near the active site of spliceosomes, which may play roles in exon ligation and mRNA release...
- Vetter D, Cohen Naftaly M, Villanueva A, Lee Y, Kocabayoglu P, Hannivoort R, et al. Enhanced hepatocarcinogenesis in mouse models and human hepatocellular carcinoma by coordinate KLF6 depletion and increased messenger RNA splicing. Hepatology. 2012;56:1361-70 pubmed publisher..Moreover, SV1 binds directly to KLF6 and accelerates its degradation. These findings represent a novel mechanism underlying the antagonism of tumor suppressor gene function by a splice variant of the same gene. ..
- Daniel C, Venø M, Ekdahl Y, Kjems J, Ohman M. A distant cis acting intronic element induces site-selective RNA editing. Nucleic Acids Res. 2012;40:9876-86 pubmed publisher..In human, thousands of genes are edited in duplexes formed by inverted repeats in non-coding regions. It is likely that numerous such duplexes can induce editing of coding regions throughout the transcriptome. ..
- ..This review focuses on recent advances in the characterization of the splicing helicases and their interactions, and highlights the deep integration of splicing helicases in global mRNP biogenesis pathways...
- Englert M, Xia S, Okada C, Nakamura A, Tanavde V, Yao M, et al. Structural and mechanistic insights into guanylylation of RNA-splicing ligase RtcB joining RNA between 3'-terminal phosphate and 5'-OH. Proc Natl Acad Sci U S A. 2012;109:15235-40 pubmed
- Albulescu L, Sabet N, Gudipati M, Stepankiw N, Bergman Z, Huffaker T, et al. A quantitative, high-throughput reverse genetic screen reveals novel connections between Pre-mRNA splicing and 5' and 3' end transcript determinants. PLoS Genet. 2012;8:e1002530 pubmed publisher..cerevisiae may more closely resemble mammalian models of exon-definition. More broadly, our work demonstrates the capacity of this approach to identify novel regulators of various cellular RNAs. ..
- Khodor Y, Menet J, Tolan M, Rosbash M. Cotranscriptional splicing efficiency differs dramatically between Drosophila and mouse. RNA. 2012;18:2174-86 pubmed publisher..The gene length and distance effects indicate that more "nascent time" gives rise to greater cotranscriptional splicing efficiency in both systems. ..
- Crawford D, Hoskins A, Friedman L, Gelles J, Moore M. Single-molecule colocalization FRET evidence that spliceosome activation precedes stable approach of 5' splice site and branch site. Proc Natl Acad Sci U S A. 2013;110:6783-8 pubmed publisher..Separation of the sites of chemistry until very late in the splicing pathway may be crucial for preventing splicing at incorrect sites. ..
- Chakravarty A, Shuman S. The sequential 2',3'-cyclic phosphodiesterase and 3'-phosphate/5'-OH ligation steps of the RtcB RNA splicing pathway are GTP-dependent. Nucleic Acids Res. 2012;40:8558-67 pubmed..The cyclic phosphodiesterase activity of RtcB depends on GTP and the formation of the RtcB-GMP adduct, signifying that RtcB guanylylation precedes the cyclic phosphodiesterase and 3'-phosphate ligase steps of the RNA splicing pathway.
- Hessle V, von Euler A, González de Valdivia E, Visa N. Rrp6 is recruited to transcribed genes and accompanies the spliced mRNA to the nuclear pore. RNA. 2012;18:1466-74 pubmed publisher..These observations suggest that the quality control of pre-mRNA splicing is not based on the selective recruitment of the exoribonuclease Rrp6 to unprocessed mRNAs. ..
- Berg M, Singh L, Younis I, Liu Q, Pinto A, Kaida D, et al. U1 snRNP determines mRNA length and regulates isoform expression. Cell. 2012;150:53-64 pubmed publisher..Additional experiments suggest cotranscriptional PCPA counteracted by U1 association with nascent transcripts, a process we term telescripting, ensuring transcriptome integrity and regulating mRNA length. ..
- Merkin J, Russell C, Chen P, Burge C. Evolutionary dynamics of gene and isoform regulation in Mammalian tissues. Science. 2012;338:1593-9 pubmed publisher..Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling. ..
- Mezlini A, Smith E, Fiume M, Buske O, Savich G, Shah S, et al. iReckon: simultaneous isoform discovery and abundance estimation from RNA-seq data. Genome Res. 2013;23:519-29 pubmed publisher..QT-PCR validations of the isoforms detected in the MCF7 cell line confirmed all of iReckon's predictions and also showed strong agreement (r(2) = 0.94) with the predicted abundances. ..