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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
N6-methyladenosine modification in mRNA: machinery, function and implications for health and diseases
1Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India.
Abstract:
N6-methyladenosine (m(6) A) modification in mRNA is extremely widespread, and functionally modulates the eukaryotic transcriptome to influence mRNA splicing, export, localization, translation, and stability. Methylated adenines are present in a large subset of mRNAs and long noncoding RNAs (lncRNAs). Methylation is reversible, and this is accomplished by the orchestrated action of highly conserved methyltransferase (m(6) A writer) and demethylase (m(6) A eraser) enzymes to shape the cellular 'epitranscriptome'. The engraved 'methyl code' is subsequently decoded and executed by a group of m(6) A reader/effector components, which, in turn, govern the fate of the modified transcripts, thereby dictating their potential for translation. Reversible mRNA methylation thus adds another layer of regulation at the post-transcriptional level in the gene expression programme of eukaryotes that finely sculpts a highly dynamic proteome in order to respond to diverse cues during cellular differentiation, immune tolerance, and neuronal signalling.
Insights
N6-methyladenosine (m(6)A) is a crucial mRNA modification affecting gene expression. This reversible process, involving m(6)A writers and erasers, regulates RNA fate and protein production.
Area of Science:
- Molecular Biology
- Epigenetics
- RNA Biology
Background:
- N6-methyladenosine (m(6)A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA) and long noncoding RNAs (lncRNAs).
- m(6)A modification plays a critical role in regulating RNA splicing, export, localization, translation, and stability.
- The dynamic and reversible nature of m(6)A methylation is essential for cellular function.
Purpose of the Study:
- To elucidate the regulatory mechanisms and functional significance of m(6)A modification in eukaryotes.
- To highlight the role of m(6)A 'writers' and 'erasers' in shaping the epitranscriptome.
- To understand how m(6)A 'readers' decode the 'methyl code' to influence gene expression.
Main Methods:
- Analysis of m(6)A modification dynamics in various cellular processes.
- Investigating the enzymatic activities of m(6)A methyltransferases and demethylases.
- Studying the function of m(6)A reader proteins in post-transcriptional regulation.
Main Results:
- m(6)A modification is widespread across eukaryotic mRNAs and lncRNAs, influencing multiple aspects of RNA metabolism.
- Reversible methylation by m(6)A writers and erasers establishes a dynamic epitranscriptome.
- m(6)A reader proteins interpret the methyl mark, controlling RNA fate and translation efficiency.
Conclusions:
- Reversible mRNA methylation represents a significant layer of post-transcriptional gene regulation in eukaryotes.
- The m(6)A regulatory network is vital for cellular differentiation, immune response, and neuronal signaling.
- Understanding m(6)A dynamics offers insights into fine-tuning proteome output for adaptive cellular functions.
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