Limited effects of m6A modification on mRNA partitioning into stress granules

Anthony Khong, Tyler Matheny, Thao Ngoc Huynh, Vincent Babl and Roy Parker ()
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Anthony Khong: University of Colorado
Tyler Matheny: University of Colorado
Thao Ngoc Huynh: University of Colorado
Vincent Babl: University of Colorado
Roy Parker: University of Colorado

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract The presence of the m6A modification in mammalian mRNAs is proposed to promote mRNA recruitment to stress granules through the interaction with YTHDF proteins. We test this possibility by examining the accumulation of mRNAs in stress granules in both WT and ∆METTL3 mES cells, which are deficient in m6A modification. A critical observation is that all m6A modified mRNAs partition similarly into stress granules in both wild-type and m6A-deficient cells by single-molecule FISH. Moreover, multiple linear regression analysis indicates m6A modification explains only 6% of the variance in stress granule localization when controlled for length. Finally, the artificial tethering of 25 YTHDF proteins on reporter mRNAs leads to only a modest increase in mRNA partitioning to stress granules. Since most mammalian mRNAs have 4 or fewer m6A sites, and those sites are not fully modified, this argues m6A modifications are unlikely to play a significant role in recruiting mRNAs to stress granules. Taken together, these observations argue that m6A modifications play a minimal, if any, role in mRNA partitioning into stress granules.

Date: 2022
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DOI: 10.1038/s41467-022-31358-5

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