MRN1 implicates chromatin remodeling complexes and architectural factors in mRNA maturation

PLoS One. 2012;7(9):e44373. doi: 10.1371/journal.pone.0044373. Epub 2012 Sep 18.

Abstract

A functional relationship between chromatin structure and mRNA processing events has been suggested, however, so far only a few involved factors have been characterized. Here we show that rsc nhp6ΔΔ mutants, deficient for the function of the chromatin remodeling factor RSC and the chromatin architectural proteins Nhp6A/Nhp6B, accumulate intron-containing pre-mRNA at the restrictive temperature. In addition, we demonstrate that rsc8-ts16 nhp6ΔΔ cells contain low levels of U6 snRNA and U4/U6 di-snRNA that is further exacerbated after two hours growth at the restrictive temperature. This change in U6 snRNA and U4/U6 di-snRNA levels in rsc8-ts16 nhp6ΔΔ cells is indicative of splicing deficient conditions. We identify MRN1 (multi-copy suppressor of rsc nhp6ΔΔ) as a growth suppressor of rsc nhp6ΔΔ synthetic sickness. Mrn1 is an RNA binding protein that localizes both to the nucleus and cytoplasm. Genetic interactions are observed between 2 µm-MRN1 and the splicing deficient mutants snt309Δ, prp3, prp4, and prp22, and additional genetic analyses link MRN1, SNT309, NHP6A/B, SWI/SNF, and RSC supporting the notion of a role of chromatin structure in mRNA processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Assembly and Disassembly / genetics
  • Chromatin Assembly and Disassembly / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • HMGN Proteins / genetics
  • HMGN Proteins / metabolism
  • Immunoblotting
  • Microscopy, Fluorescence
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spliceosomes / genetics
  • Spliceosomes / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • HMGN Proteins
  • NHP6A protein, S cerevisiae
  • NHP6B protein, S cerevisiae
  • RNA, Messenger
  • RNA, Small Nuclear
  • RSC complex, S cerevisiae
  • SNT309 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • U4 small nuclear RNA
  • U6 small nuclear RNA

Grants and funding

L.D. was supported by a Ph.D. stipend from the Faculty of Natural Sciences, University of Copenhagen, T.H.J. was supported by the Danish National Research Foundation (Grundforskningsfonden), and S.H. was supported by grants from the Danish Research Councils, The Carlsberg Foundation and Manufacturer Vilhelm Pedersen and Wife Memorial Legacy (this support was granted on recommendation from the Novo Nordisk Foundation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.