A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions

David S McPheeters1, Nicole Cremona, Sham Sunder

  • 1Center for RNA Molecular Biology and Department of Molecular Biology & Microbiology, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106-4960, USA.

Insights

Fission yeast blocks meiotic cyclin (crs1) expression in growing cells by degrading its pre-mRNA. This RNA turnover requires the exosome and Mmi1, ensuring rapid adaptation to stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Fission yeast crs1 pre-mRNA expression is blocked in actively growing cells.
  • This blockage involves a complex regulatory mechanism targeting crs1 transcripts for degradation instead of splicing and polyadenylation.

Purpose of the Study:

  • To elucidate the multifaceted mechanism responsible for blocking crs1 pre-mRNA expression in vegetative fission yeast cells.
  • To identify the factors involved in the targeted degradation of crs1 transcripts.

Main Methods:

  • Analysis of crs1 pre-mRNA processing and turnover in wild-type and mutant fission yeast strains.
  • Investigating the roles of the exosome, Mmi1, and polyadenylation factors in crs1 RNA regulation.

Main Results:

  • Vegetative crs1 transcripts are synthesized but degraded, requiring the exosome and a factor implicated in meiotic RNA turnover (Mmi1).
  • Mmi1 mutants, similar to exosome mutants, exhibit splicing and polyadenylation of vegetative crs1 transcripts.
  • Regulatory elements at the 3' end of the crs1 gene correlate with increased spliced RNA in polyadenylation factor mutants.

Conclusions:

  • A highly integrated regulatory strategy involving RNA degradation ensures crs1 repression in growing cells.
  • This mechanism allows for a rapid response to adverse conditions, contributing to cell survival.

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