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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation
Sung Ho Boo1, Hongseok Ha1, Yoon Ki Kim2
1Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
Abstract:
N6-Methyladenosine (m6A), the most abundant internal mRNA modification, affects multiple steps in gene expression. Mechanistically, the binding of YTHDF2 to m6A on mRNAs elicits rapid mRNA degradation by recruiting several RNA degrading enzymes. Here, we show that N1-methyladenosine (m1A), another type of RNA modification, accelerates rapid m6A RNA degradation. We identify HRSP12 as an RNA-binding protein that recognizes m1A. The binding of HRSP12 to m1A promotes efficient interaction of YTHDF2 with m6A, consequently facilitating endoribonucleolytic cleavage via the RNase P/MRP complex. Transcriptome-wide analyses also reveal that mRNAs harboring both m1A and m6A are downregulated in an HRSP12-dependent manner compared with mRNAs harboring m6A only. Accordingly, a subset of endogenous circular RNAs that harbor m6A and associate with YTHDF2 in an HRSP12-dependent manner is also subjected to m1A-facilitated rapid degradation. Together, our observations provide compelling evidence for crosstalk between different RNA modifications.
Insights
N1-methyladenosine (m1A) RNA modification accelerates the degradation of N6-methyladenosine (m6A) modified mRNAs. HRSP12 protein binding to m1A enhances m6A reader YTHDF2 interaction, promoting mRNA decay.
Area of Science:
- Molecular Biology
- RNA Biology
- Epigenetics
Background:
- N6-Methyladenosine (m6A) is the most prevalent internal mRNA modification, regulating gene expression.
- YTHDF2 protein binds m6A on mRNAs, leading to rapid mRNA degradation via recruited RNA-degrading enzymes.
Purpose of the Study:
- To investigate the role of N1-methyladenosine (m1A) in RNA modification pathways.
- To elucidate the mechanism by which m1A influences m6A-mediated RNA degradation.
Main Methods:
- Identification of RNA-binding proteins interacting with m1A.
- Analysis of protein-RNA interactions using transcriptome-wide approaches.
- Assessment of mRNA and circular RNA degradation dynamics.
Main Results:
- N1-methyladenosine (m1A) accelerates m6A-mediated rapid mRNA degradation.
- HRSP12 protein was identified as an m1A reader, promoting YTHDF2 binding to m6A.
- HRSP12-dependent downregulation of mRNAs and circular RNAs containing both m1A and m6A was observed.
Conclusions:
- m1A acts as a crucial regulator of m6A RNA degradation.
- Crosstalk between different RNA modifications (m1A and m6A) influences gene expression.
- HRSP12 mediates the interplay between m1A and m6A modifications to control RNA stability.
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