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The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon
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
Source PublicationPLOS GENETICS
AbstractThe 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.
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
WOS Research AreaGenetics & Heredity
WOS SubjectGenetics & Heredity
WOS IDWOS:000272419500003
Citation statistics
Cited Times:26[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.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
Recommended Citation
GB/T 7714
Liu, Yilei,Bourgeois, Cyril F.,Pang, Shaochen,et al. The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon[J]. PLOS GENETICS,2009,5(11).
APA Liu, Yilei.,Bourgeois, Cyril F..,Pang, Shaochen.,Kudla, Marek.,Dreumont, Natacha.,...&Elliott, David J..(2009).The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon.PLOS GENETICS,5(11).
MLA Liu, Yilei,et al."The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon".PLOS GENETICS 5.11(2009).
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