PMID- 36300875 OWN - NLM STAT- MEDLINE DCOM- 20221216 LR - 20221222 IS - 1521-3773 (Electronic) IS - 1433-7851 (Linking) VI - 61 IP - 52 DP - 2022 Dec 23 TI - An RNA G-Quadruplex Structure within the ADAR 5'UTR Interacts with DHX36 Helicase to Regulate Translation. PG - e202203553 LID - 10.1002/anie.202203553 [doi] AB - RNA G-quadruplex (rG4) structures in the 5' untranslated region (5'UTR) play crucial roles in fundamental cellular processes. ADAR is an important enzyme that binds to double-strand RNA and accounts for the conversion of Adenosine to Inosine in RNA editing. However, so far there is no report on the formation and regulatory role of rG4 on ADAR expression. Here, we identify and characterize a thermostable rG4 structure within the 5'UTR of the ADAR1 mRNA and demonstrate its formation and inhibitory role on translation in reporter gene and native gene constructs. We reveal rG4-specific helicase DHX36 interacts with this rG4 in vitro and in cells under knockdown and knockout conditions by GTFH (G-quadruplex-triggered fluorogenic hybridization) probes and modulates translation in an rG4-dependent manner. Our results further substantiate the rG4 structure-DHX36 protein interaction in cells and highlight rG4 to be a key player in controlling ADAR1 translation. CI - (c) 2022 Wiley-VCH GmbH. FAU - Lyu, Kaixin AU - Lyu K AUID- ORCID: 0000-0002-9330-1296 AD - Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR, China. FAU - Chen, Shuo-Bin AU - Chen SB AUID- ORCID: 0000-0001-9118-2185 AD - School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, 510006, China. FAU - Chow, Eugene Yui-Ching AU - Chow EY AUID- ORCID: 0000-0002-5575-6724 AD - School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Zhao, Haizhou AU - Zhao H AUID- ORCID: 0000-0002-2920-6219 AD - Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR, China. FAU - Yuan, Jia-Hao AU - Yuan JH AD - School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, 510006, China. FAU - Cai, Meng AU - Cai M AUID- ORCID: 0000-0002-0748-7363 AD - Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China. AD - Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, Tung Biomedical Sciences Center, City University of Hong Kong, Hong Kong SAR, China. FAU - Shi, Jiahai AU - Shi J AUID- ORCID: 0000-0002-6467-8289 AD - Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China. AD - Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, Tung Biomedical Sciences Center, City University of Hong Kong, Hong Kong SAR, China. AD - Department of Biochemistry, Synthetic Biology Translational Research Programmes, Yong Loo Lin School of Medicine, National University of, Singapore, Singapore. FAU - Chan, Ting-Fung AU - Chan TF AUID- ORCID: 0000-0002-0489-3884 AD - School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong SAR, China. FAU - Tan, Jia-Heng AU - Tan JH AUID- ORCID: 0000-0002-1612-7482 AD - School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, 510006, China. FAU - Kwok, Chun Kit AU - Kwok CK AUID- ORCID: 0000-0001-9175-8543 AD - Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR, China. AD - Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221123 PL - Germany TA - Angew Chem Int Ed Engl JT - Angewandte Chemie (International ed. in English) JID - 0370543 RN - 0 (5' Untranslated Regions) RN - 0 (RNA, Messenger) SB - IM MH - 5' Untranslated Regions MH - *G-Quadruplexes MH - RNA, Messenger/metabolism OTO - NOTNLM OT - ADAR OT - DHX36 OT - Gene Expression OT - RNA G-Quadruplex OT - Structure-Function Relationship EDAT- 2022/10/28 06:00 MHDA- 2022/12/17 06:00 CRDT- 2022/10/27 08:24 PHST- 2022/03/08 00:00 [received] PHST- 2022/10/28 06:00 [pubmed] PHST- 2022/12/17 06:00 [medline] PHST- 2022/10/27 08:24 [entrez] AID - 10.1002/anie.202203553 [doi] PST - ppublish SO - Angew Chem Int Ed Engl. 2022 Dec 23;61(52):e202203553. doi: 10.1002/anie.202203553. Epub 2022 Nov 23.