Limited effects of m6A modification on mRNA partitioning into stress granules

Anthony Khong1,2, Tyler Matheny1,3, Thao Ngoc Huynh1

  • 1Department of Biochemistry, University of Colorado, Boulder, CO, 80309, USA.

Nature Communications
|June 29, 2022
PubMed

Insights

N6-methyladenosine (m6A) modification does not significantly recruit mRNAs to cellular stress granules. This study found m6A-modified mRNAs localize similarly in both normal and m6A-deficient cells, suggesting a minimal role.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Cellular Stress Response

Background:

  • N6-methyladenosine (m6A) is a prevalent mRNA modification in mammals.
  • m6A is proposed to mediate mRNA recruitment to stress granules via YTHDF proteins.

Purpose of the Study:

  • To investigate the role of m6A modification in mRNA recruitment to stress granules.
  • To determine if m6A modification is essential for stress granule localization.

Main Methods:

  • Comparison of mRNA localization in wild-type and m6A-deficient mouse embryonic stem (mES) cells.
  • Single-molecule fluorescence in situ hybridization (smFISH) for mRNA detection.
  • Multiple linear regression analysis.
  • Reporter mRNA assays with artificial YTHDF protein tethering.

Main Results:

  • m6A-modified mRNAs showed similar partitioning into stress granules in both wild-type and m6A-deficient cells.
  • m6A modification explained only 6% of the variance in stress granule localization, independent of mRNA length.
  • Artificial tethering of YTHDF proteins resulted in only a modest increase in mRNA partitioning.

Conclusions:

  • m6A modification plays a minimal role in the recruitment of mRNAs to stress granules.
  • The proposed mechanism of YTHDF protein-mediated recruitment via m6A is unlikely to be a major driver of mRNA localization to stress granules.

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