The mechanism underlying redundant functions of the YTHDF proteins

The YTH N⁶-methyladenosine RNA binding proteins (YTHDFs) mediate the functional effects of N⁶-methyladenosine (m⁶A) 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 m⁶A dependent.