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

eLife

Se-Jin Jeong¹  Shinyeong Ju²  Cheolju Lee³  Rasmus Ree⁴  Nina McTiernan⁴  Thomas Arnesen⁵  Leah Gottlieb⁶  Ronen Marmorstein⁷  Elaine Marchi⁸  Andrew Garcia⁸  Goo Taeg Oh⁹  Hyae Yon Kweon⁹  Seong-keun Sonn⁹  Sejin Jeon⁹  Seungwoon Seo⁹  Taesoo Kim⁹  Hyun-Seok Kim⁹  Mi-Ni Lee^1,10  Tae-Young Roh^1,11  David Bolton^1,12  Simon J Conway^1,13  Michael Flory^1,14  Max Dorfel^1,15  Jonathan Crain^1,15  Ahmed Ismail^1,15  Scott Lyons^1,15  Alison Sebold^1,15  Thomas PaPazyan^1,15  Gholson J Lyon^1,16 

[1] 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;Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Republic of Korea;Department of Converging Science and Technology, KHU-KIST, Kyung Hee University, Seoul, Republic of Korea;Department of Biomedicine, University of Bergen, Bergen, Norway;Department of Biomedicine, University of Bergen, Bergen, Norway;Department of Biological Sciences, University of Bergen, Bergen, Norway;Department of Surgery, Haukeland University Hospital, Bergen, Norway;Department of Chemistry, University of Pennsylvania, Philadelphia, United States;Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States;Department of Chemistry, University of Pennsylvania, Philadelphia, United States;Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States;Department of Biochemistry and Biophysics, Perelman School of Medicine, 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 Science and College of Natural Sciences, Ewha Womans University, Seoul, Republic of Korea;Laboratory Animal Resource Center Korea ResearchInstitute of Bioscience and Biotechnology, Chungbuk, 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;Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Woodbury, United States;Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, United States;Biology PhD Program, The Graduate Center, The City University of New York, New York, United States;George A. Jervis Clinic, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, United States;

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

DOI  :  10.7554/eLife.65952

来源: eLife Sciences Publications, Ltd

【 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】

CC BY