Journalartikel

Jahr der Veröffentlichung: 2013

Seiten: e1003856-

Zeitschrift: PLoS Genetics

Bandnummer: 9

Heftnummer: 10

ISSN: 1553-7390

Open Access Status: Gold

DOI Link: https://doi.org/10.1371/journal.pgen.1003856

Verlag: Public Library of Science

Abstract: 
The U1 small nuclear ribonucleoprotein (snRNP)-specific U1C protein participates in 5' splice site recognition and regulation of pre-mRNA splicing. Based on an RNA-Seq analysis in HeLa cells after U1C knockdown, we found a conserved, intra-U1 snRNP cross-regulation that links U1C and U1-70K expression through alternative splicing and U1 snRNP assembly. To investigate the underlying regulatory mechanism, we combined mutational minigene analysis, in vivo splice-site blocking by antisense morpholinos, and in vitro binding experiments. Alternative splicing of U1-70K pre-mRNA creates the normal (exons 7-8) and a non-productive mRNA isoform, whose balance is determined by U1C protein levels. The non-productive isoform is generated through a U1C-dependent alternative 39 splice site, which requires an adjacent cluster of regulatory 5' splice sites and binding of intact U1 snRNPs. As a result of nonsense-mediated decay (NMD) of the non-productive isoform, U1-70K mRNA and protein levels are down-regulated, and U1C incorporation into the U1 snRNP is impaired. U1-70K/U1C-deficient particles are assembled, shifting the alternative splicing balance back towards productive U1-70K splicing, and restoring assembly of intact U1 snRNPs. Taken together, we established a novel feedback regulation that controls U1-70K/U1C homeostasis and ensures correct U1 snRNP assembly and function.

Harvard-Zitierstil: Rösel-Hillgärtner, T., Hung, L., Khrameeva, E., Le Querrec, P., Gelfand, M. and Bindereif, A. (2013) A Novel Intra-U1 snRNP Cross-Regulation Mechanism: Alternative Splicing Switch Links U1C and U1-70K Expression, PLoS Genetics, 9(10), p. e1003856. https://doi.org/10.1371/journal.pgen.1003856

APA-Zitierstil: Rösel-Hillgärtner, T., Hung, L., Khrameeva, E., Le Querrec, P., Gelfand, M., & Bindereif, A. (2013). A Novel Intra-U1 snRNP Cross-Regulation Mechanism: Alternative Splicing Switch Links U1C and U1-70K Expression. PLoS Genetics. 9(10), e1003856. https://doi.org/10.1371/journal.pgen.1003856