Back to Search
Start Over
Tls1 regulates splicing of shelterin components to control telomeric heterochromatin assembly and telomere length.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2014 Oct; Vol. 42 (18), pp. 11419-32. Date of Electronic Publication: 2014 Sep 22. - Publication Year :
- 2014
-
Abstract
- Heterochromatin preferentially forms at repetitive DNA elements through RNAi-mediated targeting of histone-modifying enzymes. It was proposed that splicing factors interact with the RNAi machinery or regulate the splicing of repeat transcripts to directly participate in heterochromatin assembly. Here, by screening the fission yeast deletion library, we comprehensively identified factors required for telomeric heterochromatin assembly, including a novel gene tls1+. Purification of Tls1 and mass spectrometry analysis of its interacting proteins show that Tls1 associates with the spliceosome subunit Brr2. RNA sequencing analysis shows that the splicing of a subset of mRNAs are affected in tls1Δ cells, including mRNAs of shelterin components rap1+ and poz1+. Importantly, replacing rap1+ and poz1+ with their cDNAs significantly alleviated heterochromatin defects of tls1Δ cells, suggesting that the missplicing of shelterin components is the cause of such defects, and that splicing factors regulate telomeric heterochromatin through the proper splicing of heterochromatin factors. In addition to its role in telomeric heterochromatin assembly, Tls1-mediated splicing of shelterin mRNAs also regulates telomere length. Given that its human homologue C9ORF78 also associates with the spliceosome and is overexpressed in multiple cancer cell lines, our results suggest that C9ORF78 overexpression might alter the proper splicing of genes during cancer progression.<br /> (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Nuclear Proteins genetics
Nuclear Proteins physiology
RNA Splicing Factors
Schizosaccharomyces genetics
Schizosaccharomyces metabolism
Schizosaccharomyces pombe Proteins genetics
Schizosaccharomyces pombe Proteins physiology
Spliceosomes metabolism
Telomere-Binding Proteins metabolism
Heterochromatin metabolism
Nuclear Proteins metabolism
RNA Splicing
Schizosaccharomyces pombe Proteins metabolism
Telomere metabolism
Telomere Homeostasis
Telomere-Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 42
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 25245948
- Full Text :
- https://doi.org/10.1093/nar/gku842