ArticleNucleic acids research2014
Tls1 regulates splicing of shelterin components to control telomeric heterochromatin assembly and telomere length.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Combinatorial Analyses of Pre-mRNA Splicing-Defective Mutants Reveal Differential Quantitative Requirements for Shelterin in Distinct Telomere Functions.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- A systematic quantitative approach comprehensively defines domain-specific functional pathways linked to Schizosaccharomyces pombe heterochromatin regulation.Nucleic acids research · 2024Article
- A systematic quantitative approach comprehensively defines domain-specific functional pathways linked tobioRxiv : the preprint server for biology · 2024Article
- Splicing of branchpoint-distant exons is promoted by Cactin, Tls1 and the ubiquitin-fold-activated Sde2.Nucleic acids research · 2022Article
- Facultative heterochromatin formation in rDNA is essential for cell survival during nutritional starvation.Nucleic acids research · 2022Article
- C9ORF78 partially localizes to centromeres and plays a role in chromosome segregation.Experimental cell research · 2022Article
- A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing.Nature communications · 2022Article
- Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study.Biomolecules · 2021Article
- Anti-silencing factor Epe1 associates with SAGA to regulate transcription within heterochromatin.Genes & development · 2019Article
- Intron specificity in pre-mRNA splicing.Current genetics · 2018Review
- Sde2 is an intron-specific pre-mRNA splicing regulator activated by ubiquitin-like processing.The EMBO journal · 2018Article
- Set3 contributes to heterochromatin integrity by promoting transcription of subunits of Clr4-Rik1-Cul4 histone methyltransferase complex in fission yeast.Scientific reports · 2016Article
- The proper connection between shelterin components is required for telomeric heterochromatin assembly.Genes & development · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
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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.
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