YTHDF2 facilitates aggresome formation via UPF1 in an m⁶A-independent manner.

ABSTRACT: YTHDF2 has been extensively studied and typified as an RNA-binding protein that specifically recognizes and destabilizes RNAs harboring N⁶-methyladenosine (m⁶A), the most prevalent internal modification found in eukaryotic RNAs. In this study, we unravel the m⁶A-independent role of YTHDF2 in the formation of an aggresome, where cytoplasmic protein aggregates are selectively sequestered upon failure of protein homeostasis mediated by the ubiquitin-proteasome system. Downregulation of YTHDF2 in HeLa cells reduces the circularity of aggresomes and the rate of movement of misfolded polypeptides, inhibits aggresome formation, and thereby promotes cellular apoptosis. Mechanistically, YTHDF2 is recruited to a misfolded polypeptide-associated complex composed of UP

SUBMITTER: Hwang HJ 

PROVIDER: S-EPMC10558514 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature