Stress granules are biomolecular condensates composed of protein and mRNA. One feature of stress granule-enriched mRNAs is that they are often longer than average. Another feature of stress granule-enriched mRNAs is that they often contain multiple N⁶-methyladenosine (m⁶A) residues. m⁶A is bound by the YTHDF proteins, creating mRNA–protein complexes that partition into stress granules in mammalian cells. Here we show that length-dependent enrichment of mRNAs in stress granules is mediated by m⁶A. Long mRNAs often contain one or more long exons, which are preferential sites of m⁶A formation. In mammalian cells lacking m⁶A, long mRNAs no longer show preferential stress granule enrichment. Furthermore, we show that m⁶A abundance more strongly predicts which short or long mRNAs are enriched in stress granules, rather than length alone. Thus, mRNA length correlates with mRNA enrichment in stress granules owing to the high prevalence of m⁶A in long mRNAs.

应激颗粒是由蛋白质和 mRNA 组成的生物分子凝聚物。富含应激颗粒的 mRNA 的一个特征是它们通常比平均长度长。富含应激颗粒的 mRNA 的另一个特征是它们通常包含多个 N⁶-甲基腺苷 （m⁶A） 残基。m⁶A 与 YTHDF 蛋白结合，产生 mRNA-蛋白质复合物，在哺乳动物细胞中分配成应激颗粒。在这里，我们表明应激颗粒中 mRNA 的长度依赖性富集是由 m⁶A 介导的。长 mRNA 通常包含一个或多个长外显子，它们是 m⁶A 形成的优先位点。在缺乏 m⁶A 的哺乳动物细胞中，长 mRNA 不再显示出优先的应激颗粒富集。此外，我们表明 m⁶A 丰度更强烈地预测哪些短或长 mRNA 富集于应激颗粒中，而不仅仅是长度。因此，由于 m⁶A 在长 mRNA 中的普遍性很高，因此 mRNA 长度与应激颗粒中 mRNA 的富集相关。