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N6-methyl-adenosine modification in messenger and long non-coding RNA
1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. taopan@uchicago.edu
Abstract:
N6-methyl-adenosine (m(6)A) is the most abundant modification in mammalian mRNA and long non-coding RNA. First discovered in the 1970s, m(6)A modification has been proposed to function in mRNA splicing, export, stability, and immune tolerance. Interest and excitement in m(6)A modification has recently been revived based on the discovery of a mammalian enzyme that removes m(6)A and the application of deep sequencing to localize modification sites. The m(6)A demethylase fat mass and obesity associated protein (FTO) controls cellular energy homeostasis and is the first enzyme discovered that reverses an RNA modification. m(6)A Sequencing demonstrates cell-type- and cell-state-dependent m(6)A patterns, indicating that m(6)A modifications are highly regulated. This review describes the current knowledge of mammalian m(6)A modifications and future perspectives on how to push the field forward.
Insights
N6-methyl-adenosine (m(6)A) is a key RNA modification involved in gene regulation. Recent discoveries, including the FTO demethylase and m(6)A sequencing, highlight its dynamic and cell-specific nature.
Area of Science:
- Molecular Biology
- Epigenetics
- RNA Biology
Background:
- N6-methyl-adenosine (m(6)A) is the most prevalent epitranscriptomic mark in mammalian messenger RNA (mRNA) and long non-coding RNA (lncRNA).
- m(6)A modifications are implicated in crucial RNA processing events including splicing, nuclear export, stability, and immune response modulation.
- Recent advancements, such as the identification of m(6)A-removing enzymes and deep sequencing techniques, have revitalized interest in m(6)A regulation.
Purpose of the Study:
- To review the current understanding of mammalian m(6)A modifications.
- To discuss the role of the m(6)A demethylase, fat mass and obesity associated protein (FTO), in cellular energy homeostasis.
- To highlight the dynamic and regulated nature of m(6)A patterns across different cell types and states.
Main Methods:
- Literature review of m(6)A research.
- Discussion of m(6)A sequencing technologies for mapping modification sites.
- Analysis of the enzymatic activity of FTO in reversing m(6)A marks.
Main Results:
- m(6)A modifications are highly regulated and exhibit cell-type- and cell-state-specific patterns.
- The m(6)A demethylase FTO plays a significant role in controlling cellular energy homeostasis.
- Deep sequencing methods enable precise localization of m(6)A modification sites.
Conclusions:
- m(6)A modification is a critical regulatory mechanism in mammalian cells.
- Further research into m(6)A is essential for understanding gene expression and cellular functions.
- Future perspectives focus on advancing the field of m(6)A research and its implications.
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