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Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
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Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules

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m6A governs length-dependent enrichment of mRNAs in stress granules

Ryan J Ries1, Brian F Pickering1, Hui Xian Poh1

  • 1Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA.

Nature Structural & Molecular Biology
|September 14, 2023
PubMed

Insights

N6-methyladenosine (m6A) drives the preferential accumulation of long messenger RNAs (mRNAs) in cellular stress granules. This finding reveals m6A as a key regulator of mRNA localization within stress granules, independent of length alone.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • RNA Biology

Background:

  • Stress granules are dynamic cytoplasmic foci formed under cellular stress.
  • Messenger RNAs (mRNAs) within stress granules are often longer and enriched with N6-methyladenosine (m6A) modifications.
  • YTHDF proteins bind m6A-modified mRNAs, facilitating their recruitment into stress granules.

Purpose of the Study:

  • To investigate the role of m6A in the length-dependent enrichment of mRNAs in stress granules.
  • To determine if m6A mediates the preferential localization of long mRNAs to stress granules.

Main Methods:

  • Analysis of mRNA enrichment in stress granules in wild-type and m6A-deficient mammalian cells.
  • Correlation analysis between mRNA length, m6A abundance, and stress granule localization.
  • Investigating the role of long exons in m6A formation and subsequent mRNA partitioning.

Main Results:

  • The length-dependent enrichment of mRNAs in stress granules is mediated by m6A.
  • In cells lacking m6A, long mRNAs lose their preferential enrichment in stress granules.
  • m6A abundance is a stronger predictor of stress granule enrichment than mRNA length alone.

Conclusions:

  • mRNA length correlates with stress granule enrichment primarily due to the higher prevalence of m6A in longer transcripts.
  • m6A modification is a critical determinant of mRNA localization to stress granules, influencing cellular stress responses.

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