Title

Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing.

Document Type

Article

Publication Date

5-20-2021

Publication Title

Molecular cell

Keywords

JMG

JAX Source

Mol Cell 2021 May 20; 81(10):2112-2122.e7

Volume

81

Issue

10

First Page

2112

Last Page

2122

ISSN

1097-4164

PMID

33909987

DOI

https://doi.org/10.1016/j.molcel.2021.03.004

Abstract

Incompletely synthesized nascent chains obstructing large ribosomal subunits are targeted for degradation by ribosome-associated quality control (RQC). In bacterial RQC, RqcH marks the nascent chains with C-terminal alanine (Ala) tails that are directly recognized by proteasome-like proteases, whereas in eukaryotes, RqcH orthologs (Rqc2/NEMF [nuclear export mediator factor]) assist the Ltn1/Listerin E3 ligase in nascent chain ubiquitylation. Here, we study RQC-mediated proteolytic targeting of ribosome stalling products in mammalian cells. We show that mammalian NEMF has an additional, Listerin-independent proteolytic role, which, as in bacteria, is mediated by tRNA-Ala binding and Ala tailing. However, in mammalian cells Ala tails signal proteolysis indirectly, through a pathway that recognizes C-terminal degrons; we identify the CRL2

Comments

We thank Rick Maser from the JAX Genetic Engineering Technologies group.

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