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Updated: Aug 8, 2026

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
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.
Abstract:
Despite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare. Here, we provide multiple lines of evidence to show that Ime4p, an N6-methyladenosine (m6A) methyltransferase required for meiosis in yeast, acts by methylating a site in the 3' UTR of the mRNA encoding Rme1p, a transcriptional repressor of meiosis. Consistent with this mechanism, genetic analyses reveal that IME4 functions upstream of RME1. Transcriptome-wide, RME1 is the primary message that displays both increased methylation and reduced expression in an Ime4p-dependent manner. In yeast strains for which IME4 is dispensable for meiosis, a natural polymorphism in the RME1 promoter reduces RME1 transcription, obviating the requirement for methylation. Mutation of a single m6A site in the RME1 3' UTR increases Rme1p repressor production and reduces meiotic efficiency. These results reveal the molecular and physiological consequences of a modification in the 3' UTR of an mRNA.
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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