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题名: The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon
作者: Liu, Yilei1; Bourgeois, Cyril F.2, 3, 4, 5; Pang, Shaochen6; Kudla, Marek7; Dreumont, Natacha2, 3, 4, 5; Kister, Liliane2, 3, 4, 5; Sun, Yong-Hua6; Stevenin, James2, 3, 4, 5; Elliott, David J.1
刊名: PLOS GENETICS
发表日期: 2009-11-01
DOI: 10.1371/journal.pgen.1000707
卷: 5, 期:11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
英文摘要: The human testis has almost as high a frequency of alternative splicing events as brain. While not as extensively studied as brain, a few candidate testis-specific splicing regulator proteins have been identified, including the nuclear RNA binding proteins RBMY and hnRNP G-T, which are germ cell-specific versions of the somatically expressed hnRNP G protein and are highly conserved in mammals. The splicing activator protein Tra2 beta is also highly expressed in the testis and physically interacts with these hnRNP G family proteins. In this study, we identified a novel testis-specific cassette exon TLE4-T within intron 6 of the human transducing-like enhancer of split 4 (TLE4) gene which makes a more transcriptionally repressive TLE4 protein isoform. TLE4-T splicing is normally repressed in somatic cells because of a weak 59 splice site and surrounding splicing-repressive intronic regions. TLE4-T RNA pulls down Tra2 beta and hnRNP G proteins which activate its inclusion. The germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. Tra2b bound moderately to TLE4-T RNA, but more strongly to upstream sites to potently activate an alternative 3' splice site normally weakly selected in the testis. Co-expression of Tra2 beta with either hnRNP G-T or RBMY re-established the normal testis physiological splicing pattern of this exon. Although they can directly bind pre-mRNA sequences around the TLE4-T exon, RBMY and hnRNP G-T function as efficient germ cell-specific splicing co-activators of TLE4-T. Our study indicates a delicate balance between the activity of positive and negative splicing regulators combinatorially controls physiological splicing inclusion of exon TLE4-T and leads to modulation of signalling pathways in the testis. In addition, we identified a high-affinity binding site for hnRNP G-T protein, showing it is also a sequence-specific RNA binding protein.
关键词[WOS]: CANDIDATE SPERMATOGENESIS GENE ; ALTERNATIVE SPLICING EVENTS ; PRE-MESSENGER-RNA ; BETA-CATENIN ; Y-CHROMOSOME ; EXPRESSION ; GROUCHO ; BINDING ; INTERACTS ; TRA2-BETA
语种: 英语
WOS记录号: WOS:000272419500003
ISSN号: 1553-7390
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/27371
Appears in Collections:鱼类生物学及渔业生物技术研究中心_期刊论文

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作者单位: 1.Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England
2.IGBMC, Dept Funct Genom, Illkirch Graffenstaden, France
3.INSERM, U964, Illkirch Graffenstaden, France
4.CNRS, UMR 7104, Illkirch Graffenstaden, France
5.Univ Strasbourg, Strasbourg, France
6.Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Beijing, Peoples R China
7.Univ Warsaw, Dept Genet, PL-00325 Warsaw, Poland
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