m6A modification of a 3' UTR site reduces RME1 mRNA levels to promote meiosis

G Guy Bushkin1,2, David Pincus3,4, Jeffrey T Morgan3,5,6

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA. gbushkin@wi.mit.edu.

Nature Communications
|August 1, 2019
PubMed

Insights

Yeast meiosis relies on Ime4p, an enzyme that modifies mRNA. This enzyme targets the RME1 mRNA

Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Messenger RNA (mRNA) modifications play crucial roles in gene regulation, but their functional consequences are often poorly understood.
  • N6-methyladenosine (m6A) is a prevalent mRNA modification, yet its specific roles in complex biological processes like meiosis are still being elucidated.
  • Identifying specific mRNA targets and the physiological impact of m6A modification is essential for understanding gene expression control.

Purpose of the Study:

  • To investigate the function of Ime4p, a methyltransferase essential for meiosis in yeast.
  • To identify the specific mRNA target of Ime4p and elucidate the mechanism by which it regulates meiotic progression.
  • To determine the molecular and physiological consequences of m6A modification on a target mRNA and its encoded protein.

Main Methods:

  • Genetic analysis of IME4 and RME1 in yeast meiosis.
  • Transcriptome-wide analysis of mRNA methylation and expression.
  • Site-directed mutagenesis of the m6A site in RME1 3' UTR.
  • Measurement of Rme1p protein levels and meiotic efficiency.

Main Results:

  • Ime4p, an N6-methyladenosine (m6A) methyltransferase, targets the mRNA encoding Rme1p, a transcriptional repressor of meiosis.
  • Methylation of RME1 mRNA by Ime4p occurs in the 3' UTR and leads to reduced RME1 expression.
  • Mutation of the m6A site in RME1 3' UTR increases Rme1p production and impairs meiotic efficiency.
  • Genetic evidence shows IME4 functions upstream of RME1, and RME1 is the primary message affected by Ime4p-dependent methylation and expression changes.

Conclusions:

  • This study reveals the direct molecular and physiological consequences of an m6A modification in the 3' UTR of an mRNA.
  • Ime4p-mediated m6A modification of RME1 mRNA is a critical regulatory mechanism controlling meiotic progression in yeast.
  • The findings highlight the importance of specific mRNA modifications in regulating gene expression and cellular processes, even when genetic variations exist.

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