The mechanism underlying the “unified model” of YTHDF proteins

The YTH N6-methyladenosine RNA Binding Proteins (YTHDFs) mediate the functions of N6-methyladenosine (m6A) in 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 this causes different behaviors in condensate formation and subsequent physiological functions. Biologically, we find that the global stabilization of RNA after depletion of all YTHDFs is a result of increased P-body formation and is independent of mRNA m6A methylation. Overall design: [Dataset 1] 10 samples. Duplicates for RNA-Seq samples with ERCC spike-in calibration in HeLa cells transfected with siRNAs targeting different genes (Non-targeting control, YTHDF1, YTHDF2, YTHDF3 and YTHDF1-3) [Dataset 2] 6 samples. Duplicates for RNA-Seq samples with ERCC spike-in calibration in HeLa cells transfected with siRNAs targeting different genes (Non-targeting control, DDX6 and DDX6/YTHDF1-3) [Dataset 3] 6 samples. Duplicates for P-body isolations with two different antibodies (EDC3 and EDC4). RNA-sq were performed