Universität zu Köln

Cerullo, Federico ORCID: 0000-0002-6042-7810, Filbeck, Sebastian ORCID: 0000-0001-5729-4538, Patil, Pratik Rajendra, Hung, Hao-Chih, Xu, Haifei, Vornberger, Julia, Hofer, Florian W., Schmitt, Jaro ORCID: 0000-0001-6701-7112, Kramer, Guenter, Bukau, Bernd ORCID: 0000-0003-0521-7199, Hofmann, Kay, Pfeffer, Stefan and Joazeiro, Claudio A. P. (2022). Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue. Nature, 603 (7901). S. 509 - 539. BERLIN: NATURE PORTFOLIO. ISSN 1476-4687

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Abstract

Ribosome stalling during translation is detrimental to cellular fitness, but how this is sensed and elicits recycling of ribosomal subunits and quality control of associated mRNA and incomplete nascent chains is poorly understood(1,2). Here we uncover Bacillus subtilis MutS2, a member of the conserved MutS family of ATPases that function in DNA mismatch repair(3), as an unexpected ribosome-binding protein with an essential function in translational quality control. Cryo-electron microscopy analysis of affinity-purified native complexes shows that MutS2 functions in sensing collisions between stalled and translating ribosomes and suggests how ribosome collisions can serve as platforms to deploy downstream processes: MutS2 has an RNA endonuclease small MutS-related (SMR) domain, as well as an ATPase/clamp domain that is properly positioned to promote ribosomal subunit dissociation, which is a requirement both for ribosome recycling and for initiation of ribosome-associated protein quality control (RQC). Accordingly, MutS2 promotes nascent chain modification with alanine-tail degrons-an early step in RQC-in an ATPase domain-dependent manner. The relevance of these observations is underscored by evidence of strong co-occurrence of MutS2 and RQC genes across bacterial phyla. Overall, the findings demonstrate a deeply conserved role for ribosome collisions in mounting a complex response to the interruption of translation within open reading frames.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cerullo, Federico UNSPECIFIED orcid.org/0000-0002-6042-7810 UNSPECIFIED Filbeck, Sebastian UNSPECIFIED orcid.org/0000-0001-5729-4538 UNSPECIFIED Patil, Pratik Rajendra UNSPECIFIED UNSPECIFIED UNSPECIFIED Hung, Hao-Chih UNSPECIFIED UNSPECIFIED UNSPECIFIED Xu, Haifei UNSPECIFIED UNSPECIFIED UNSPECIFIED Vornberger, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofer, Florian W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt, Jaro UNSPECIFIED orcid.org/0000-0001-6701-7112 UNSPECIFIED Kramer, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bukau, Bernd UNSPECIFIED orcid.org/0000-0003-0521-7199 UNSPECIFIED Hofmann, Kay UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfeffer, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Joazeiro, Claudio A. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-682359
DOI:	10.1038/s41586-022-04487-6
Journal or Publication Title:	Nature
Volume:	603
Number:	7901
Page Range:	S. 509 - 539
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	1476-4687
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language QUALITY-CONTROL; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BINDING; VISUALIZATION; SURVEILLANCE; PATHWAYS; SYSTEM Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68235