M6a Alters Ribosome Dynamics To Initiate Mrna Degradation Shino Murakami Anthony O Olareringeorge Jianheng Fox Liu Sara Zaccara Ben Hawley Samie R Jaffrey by Shino Murakami & Anthony O. Olarerin-george & Jianheng Fox Liu & Sara Zaccara & Ben Hawley & Samie R. Jaffrey 101016/JCELL202504020 instant download after payment.

SUMMARY

Degradation of mRNA containing N6-methyladenosine (m6A) is essential for cell growth, differentiation, andstress responses. Here, we show that m6A markedly alters ribosome dynamics and that these alterationsmediate the degradation effect of m6A on mRNA. We find that m6A is a potent inducer of ribosome stalling,and these stalls lead to ribosome collisions that form a unique conformation unlike those seen in other contexts. We find that the degree of ribosome stalling correlates with m6A-mediated mRNA degradation, andincreasing the persistence of collided ribosomes correlates with enhanced m6A-mediated mRNA degradation. Ribosome stalling and collision at m6A is followed by recruitment of YTHDF m6A reader proteins to promote mRNA degradation. We show that mechanisms that reduce ribosome stalling and collisions, such astranslation suppression during stress, stabilize m6A-mRNAs and increase their abundance, enabling stressresponses. Overall, our study reveals the ribosome as the initial m6A sensor for beginning m6A-mRNAdegradation.