Naa12 compensates for Naa10 in mice in the amino-terminal acetylation pathway
Abstract
Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lacking Naa10 show no globally apparent in vivo amino-terminal acetylation impairment and do not exhibit complete embryonic lethality. Rather Naa10 nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism and urogenital anomalies. Naa12 is a previously unannotated Naa10-like paralogue with NAT activity that genetically compensates for Naa10. Mice deficient for Naa12 have no apparent phenotype, whereas mice deficient for Naa10 and Naa12 display embryonic lethality. The discovery of Naa12 adds to the currently known machinery involved in amino-terminal acetylation in mice.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.Mass spectrometry data were uploaded to PRIDE under Project Name: Naa10 mutant mouse N-terminome LC-MS, Project accession: PXD026410.
Article and author information
Author details
Funding
National Research Foundation of Korea (2020R1A3B2079811)
- Gootaeg Oh
Norwegian Cancer Society (PR-2009-0222)
- Thomas Arnesen
National Research Foundation of Korea (2017RIDIAB03032286)
- Mi-Ni Lee
National Research Foundation of Korea (2020RICIC1007686)
- Mi-Ni Lee
National Institute of General Medical Sciences (R35GM133408)
- Gholson J Lyon
National Institute of General Medical Sciences (R35GM118090)
- Ronen Marmorstein
Research Council of Norway (Project 249843)
- Thomas Arnesen
National Institutes of Health (Project 249843)
- Simon J Conway
Norwegian Health Authorities of Western Norway (912176)
- Thomas Arnesen
Norwegian Health Authorities of Western Norway (F-12540-D11382)
- Thomas Arnesen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hening Lin, Cornell University, United States
Ethics
Animal experimentation: All experiments were performed in accordance with guidelines of International Animal Care and Use Committee (IACUC) of Ewha Womans University (protocol #18 012)012), Cold Spring Harbor L aboratory (CSHL) protocol # 579961 18 , and Institute for Basic Research in Developmental Disabilities (IBR) (protocol #456).
Version history
- Preprint posted: December 20, 2020 (view preprint)
- Received: December 20, 2020
- Accepted: August 5, 2021
- Accepted Manuscript published: August 6, 2021 (version 1)
- Accepted Manuscript updated: August 11, 2021 (version 2)
- Version of Record published: August 19, 2021 (version 3)
Copyright
© 2021, Kweon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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