m6a governs length-dependent enrichment of mRNAs in stress granules

Abstract

Stress granules are biomolecular condensates composed of protein and mRNA. Long mRNAs are enriched in stress granules, which is thought to reflect the ability of long mRNAs to form multiple RNA-RNA interactions with other mRNAs. RNA-RNA interactions are thus thought to be critical for stress granule formation. Stress granule-enriched mRNAs also often contain multiple N6-methyladenosine (m6A) residues. YTHDF proteins bind m6A, creating mRNA-protein complexes that partition into stress granules. Here we determine the basis of length-dependent enrichment of mRNAs in stress granules. We show that depletion of m6A is sufficient to abrogate the length-dependent enrichment of mRNAs in stress granules. We show that the presence of m6A predicts which mRNAs are enriched. m6A formation is triggered by long exons, which are often found in long mRNAs, accounting for the link between m6A, length and stress granule enrichment. Thus, length-dependent enrichment of mRNAs in stress granules is driven by YTHDF-mRNA interactions.