The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast

Scott P. Kallgren, Stuart Andrews, Xavier Tadeo, Haitong Hou, James J. Moresco, Patricia G. Tu, John R. Yates, Peter L. Nagy, Songtao Jia

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Heterochromatin preferentially assembles at repetitive DNA elements, playing roles in transcriptional silencing, recombination suppression, and chromosome segregation. The RNAi machinery is required for heterochromatin assembly in a diverse range of organisms. In fission yeast, RNA splicing factors are also required for pericentric heterochromatin assembly, and a prevailing model is that splicing factors provide a platform for siRNA generation independently of their splicing activity. Here, by screening the fission yeast deletion library, we discovered four novel splicing factors that are required for pericentric heterochromatin assembly. Sequencing total cellular RNAs from the strongest of these mutants, cwf14Δ, showed intron retention in mRNAs of several RNAi factors. Moreover, introducing cDNA versions of RNAi factors significantly restored pericentric heterochromatin in splicing mutants. We also found that mutations of splicing factors resulted in defective telomeric heterochromatin assembly and mis-splicing the mRNA of shelterin component Tpz1, and that replacement of tpz1+ with its cDNA partially rescued heterochromatin defects at telomeres in splicing mutants. Thus, proper splicing of RNAi and shelterin factors contributes to heterochromatin assembly at pericentric regions and telomeres.

Original languageEnglish (US)
Article numbere1004334
JournalPLoS genetics
Volume10
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Kallgren, S. P., Andrews, S., Tadeo, X., Hou, H., Moresco, J. J., Tu, P. G., Yates, J. R., Nagy, P. L., & Jia, S. (2014). The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast. PLoS genetics, 10(5), [e1004334]. https://doi.org/10.1371/journal.pgen.1004334