气候变化领域集成服务门户(CCPortal): Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms

CCPortal

DOI	10.1073/pnas.2021757118
	Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms
	Sun T.; Yu Y.; Wu X.; Acevedo A.; Luo J.-D.; Wang J.; Schneider W.M.; Hurwitz B.; Rosenberg B.R.; Chung H.; Rice C.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Human adenosine deaminase acting on RNA 1 (ADAR1) catalyzes adenosine-to-inosine deamination reactions on double-stranded RNA molecules to regulate cellular responses to endogenous and exogenous RNA. Defective ADAR1 editing leads to disorders such as Aicardi-Goutières syndrome, an autoinflammatory disease that manifests in the brain and skin, and dyschromatosis symmetrica hereditaria, a skin pigmentation disorder. Two ADAR1 protein isoforms, p150 (150 kDa) and p110 (110 kDa), are expressed and can edit RNA, but the contribution of each isoform to the editing landscape remains unclear, largely because of the challenges in expressing p150 without p110. In this study, we demonstrate that p110 is coexpressed with p150 from the canonical p150-encoding mRNA due to leaky ribosome scanning downstream of the p150 start codon. The presence of a strong Kozak consensus context surrounding the p110 start codon suggests the p150 mRNA is optimized to leak p110 alongside expression of p150. To reduce leaky scanning and translation initiation at the p110 start codon, we introduced synonymous mutations in the coding region between the p150 and p110 start codons. Cells expressing p150 constructs with these mutations produced significantly reduced levels of p110. Editing analysis of total RNA from ADAR1 knockout cells reconstituted separately with modified p150 and p110 revealed that more than half of the A-to-I edit sites are selectively edited by p150, and the other half are edited by either p150 or p110. This method of isoform-selective editing analysis, making use of the modified p150, has the potential to be adapted for other cellular contexts. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ADAR1 \| p110 \| p150 \| RNA editing
语种	英语
scopus关键词	adenosine deaminase acting on RNA 1; binding protein; messenger RNA; protein p110; protein p150; unclassified drug; Article; consensus sequence; controlled study; CRISPR-CAS9 system; exon; gene deletion; gene editing; gene mutation; gene silencing; human; human cell; immunoblotting; polymerase chain reaction; priority journal; protein expression; protein modification; ribosome; start codon; translation initiation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180136
作者单位	Laboratory of Virology and Infectious Disease, Rockefeller University, New York, NY 10065, United States; Bioinformatics Resource Center, Rockefeller University, New York, NY 10065, United States; Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10065, United States; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States
推荐引用方式 GB/T 7714	Sun T.,Yu Y.,Wu X.,et al. Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms[J],2021,118(12).
APA	Sun T..,Yu Y..,Wu X..,Acevedo A..,Luo J.-D..,...&Rice C.M..(2021).Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Sun T.,et al."Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).