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Structures and mechanisms of the RNA m 6A writer

Ting Deng, Jinbiao Ma

    Acta Biochimica Et Biophysica Sinica
    |September 6, 2024
    PubMed

    Insights

    N6-methyladenosine (m6A) is a key epigenetic mark on mRNA. This review details the structure and function of m6A writers, exploring how they selectively modify RNA substrates to regulate gene expression.

    Area of Science:

    • Molecular Biology
    • Epigenetics
    • RNA Biology

    Background:

    • N6-methyladenosine (m6A) is the most abundant epigenetic modification in eukaryotic messenger RNAs (mRNAs).
    • m6A modification is critical for regulating gene expression by impacting various mRNA metabolism processes.
    • The m6A machinery comprises catalytic (m6A-METTL complex) and regulatory (m6A-METTL-associated complex) subunits.

    Purpose of the Study:

    • To review recent advancements in understanding the structural and functional characteristics of m6A writers.
    • To elucidate the mechanisms by which m6A writers recognize RNA substrates.
    • To explore the selective m6A modification processes.

    Main Methods:

    • Literature review of recent research on m6A writers.
    • Analysis of structural and functional data for m6A writer complexes.
    • Examination of proposed mechanisms for RNA substrate recognition and modification.

    Main Results:

    • Detailed description of the m6A writer complexes, including METTL3/METTL14 (MTC) and associated proteins (HAKAI, WTAP, VIRMA, ZC3H13, RBM15/15B) (MACOM).
    • Insights into the structural basis for m6A writer activity.
    • Elucidation of factors influencing RNA substrate specificity.

    Conclusions:

    • m6A writers are complex molecular machines with distinct catalytic and regulatory components.
    • Understanding the structure-function relationships of m6A writers is key to deciphering their roles in gene regulation.
    • Further research into m6A modification mechanisms will provide deeper insights into epigenetic control of gene expression.

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