Naa12 compensates for Naa10 in mice in the amino-terminal acetylation pathway

eLife

Nina McTiernan¹  Ronen Marmorstein²  Max Dorfel³  Shinyeong Ju⁴  Taesoo Kim⁵  Thomas Arnesen⁵  Gholson J Lyon⁶  David Bolton⁶  Andrew Garcia⁶  Thomas PaPazyan⁷  Se-Jin Jeong⁸  Jonathan Crain⁸  Cheolju Lee⁹  Tae-Young Roh⁹  Simon J Conway⁹  Sejin Jeon⁹  Mi-Ni Lee⁹  Hyae Yon Kweon⁹  Leah Gottlieb⁹  Goo Taeg Oh^1,10  Michael Flory^1,11  Hyun-Seok Kim^1,12  Alison Sebold^1,13  Rasmus Ree^1,14  Seungwoon Seo^1,14  Ahmed Ismail^1,14  Seong-keun Sonn^1,14  Scott Lyons^1,14  Elaine Marchi^1,14 

[1] Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States;Department of Converging Science and Technology, KHU-KIST, Kyung Hee University, Seoul, Republic of Korea;Laboratory Animal Resource Center Korea ResearchInstitute of Bioscience and Biotechnology, Chungbuk, Republic of Korea;Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, United States;Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Republic of Korea;Department of Biomedicine, University of Bergen, Bergen, Norway;Department of Chemistry, University of Pennsylvania, Philadelphia, United States;Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, United States;Department of Life Science and College of Natural Sciences, Ewha Womans University, Seoul, Republic of Korea;Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea;Department of Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, United States;Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, United States;Research Design and Analysis Service, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, United States;Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Woodbury, United States;

关键词: N-terminal acetylation;    NAA10;    protein modification;    NAA12;    embryonic lethality;    hydrocephaly;   

DOI  :  10.7554/eLife.65952

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown