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 paralog 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.
| Original language | English |
|---|---|
| Article number | e65952 |
| Journal | eLife |
| Volume | 10 |
| DOIs | |
| State | Published - Aug 2021 |
Bibliographical note
Funding Information:This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean Government (2020R1A3B2079811 (GO), 2017RIDIAB03032286 (ML), and 2020RICIC1007686 (ML)). Research reported in this publication was also supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Numbers R35GM133408 (GJL) and R35GM118090 (RM), and NIH grant HL148165 (SJC). The work was also supported by the Research Council of Norway (Project 249843), the Norwegian Health Authorities of Western Norway (projects 912176 and F-12540-D11382), and the Norwegian Cancer Society (PR-2009-0222). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding was also provided by the Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratory, the George A Jervis Clinic and the Department of Human Genetics, Laboratory of Genomic Medicine at the New York State Institute for Basic Research in Developmental Disabilities (IBR), New York State Office for People with Developmental Disabilities. Part of the work was carried out at the Proteomics Unit at University of Bergen (PROBE).
Funding Information:
This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean Government (2020R1A3B2079811 (GO), 2017RIDIAB03032286 (ML), and 2020RICIC1007686 (ML)). Research reported in this publication was also supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Numbers R35GM133408 (GJL) and R35GM118090 (RM), and NIH grant HL148165 (SJC). The work was also supported by the Research Council of Norway (Project 249843), the Norwegian Health Authorities of Western Norway (projects 912176 and F-12540-D11382), and the Norwegian Cancer Society (PR-2009-0222). The con-tent is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding was also provided by the Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratory, the George A Jervis Clinic and the Department of Human Genetics, Laboratory of Genomic Medicine at the New York State Institute for Basic Research in Developmental Disabilities (IBR), New York State Office for People with Developmental Disabilities. Part of the work was carried out at the Proteomics Unit at University of Bergen (PROBE).
Publisher Copyright:
© Kweon et al.