RT Journal Article
SR Electronic
T1 Mechanistic insights into the UFM1 E3 ligase complex in ufmylation and ribosome-associated protein quality control
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.16.528878
DO 10.1101/2023.02.16.528878
A1 Ryosuke Ishimura
A1 Sota Ito
A1 Gaoxin Mao
A1 Satoko Komatsu-Hirota
A1 Toshifumi Inada
A1 Nobuo N Noda
A1 Masaaki Komatsu
YR 2023
UL http://biorxiv.org/content/early/2023/02/16/2023.02.16.528878.abstract
AB Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein covalently conjugated with intracellular proteins through ufmylation, similar to ubiquitylation. Ufmylation is involved in processes such as endoplasmic reticulum (ER)-associated protein degradation, ribosome-associated protein quality control (RQC) at the ER (ER-RQC), and ER-phagy. However, it remains unclear how ufmylation regulates such distinct ER-related functions. Herein, we provide insights into the mechanism of the UFM1 E3 complex in not only ufmylation but also ER-RQC. The E3 complex consisting of UFL1 and UFBP1 interacted with UFC1, UFM1 E2, and subsequently CDK5RAP3, the last of which is an adaptor for ufmylating ribosomal subunit RPL26. When CDK5RAP3 was absent from the E3 complex, UFBP1 ufmylation occurred, a process thought to drive ER-phagy. Further, upon treatment with anisomycin, an inducer of disome formation, the UFM1 E3 complex associated with ufmylated RPL26 on the 60S ribosomal subunit through the UFM1-interacting region of UFBP1. Loss of E3 components or disruption of the interaction between UFBP1 and ufmylated RPL26 attenuated ER-RQC. These results clarify the molecular mechanism of the UFM1 system and provide new insights into the role of ufmylation.Competing Interest StatementThe authors have declared no competing interest.