Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA.
Genome Biol. 2023 Jan 24;24(1):17. doi: 10.1186/s13059-023-02862-8.
The YTH N-methyladenosine RNA binding proteins (YTHDFs) mediate the functional effects of N-methyladenosine (mA) on RNA. Recently, a report proposed that all YTHDFs work redundantly to facilitate RNA decay, raising questions about the exact functions of individual YTHDFs, especially YTHDF1 and YTHDF2. We show that YTHDF1 and YTHDF2 differ in their low-complexity domains (LCDs) and exhibit different behaviors in condensate formation and subsequent physiological functions. Biologically, we also find that the global stabilization of RNA after depletion of all YTHDFs is driven by increased P-body formation and is not strictly mA dependent.
YTH N6-甲基腺嘌呤 RNA 结合蛋白（YTHDFs）介导 N6-甲基腺嘌呤（m6A）对 RNA 的功能影响。最近，有报道提出所有 YTHDFs 都具有冗余功能以促进 RNA 降解，这引发了对单个 YTHDFs，特别是 YTHDF1 和 YTHDF2 的确切功能的质疑。我们发现 YTHDF1 和 YTHDF2 在其低复杂度结构域（LCDs）上存在差异，并在液滴形成和随后的生理功能中表现出不同的行为。在生物学上，我们还发现，在耗尽所有 YTHDFs 后，RNA 的全局稳定性是由 P 体形成增加驱动的，并且并不严格依赖于 m6A。
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