An RNA G-Quadruplex Structure within the ADAR 5’UTR Interacts with DHX36 Helicase to Regulate Translation

Kaixin Lyu; Shuo-Bin Chen; Eugene Yui-Ching Chow; Haizhou Zhao; Jia-Hao Yuan; Meng Cai; Jiahai Shi; Ting-Fung Chan; Jia-Heng Tan; Chun Kit Kwok

doi:10.1002/anie.202203553

An RNA G-Quadruplex Structure within the ADAR 5’UTR Interacts with DHX36 Helicase to Regulate Translation

Kaixin Lyu, Shuo-Bin Chen, Eugene Yui-Ching Chow, Haizhou Zhao, Jia-Hao Yuan, Meng Cai, Jiahai Shi, Ting-Fung Chan, Jia-Heng Tan, Chun Kit Kwok^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

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.

Original language	English
Article number	e202203553
Journal	Angewandte Chemie (International Edition)
Volume	61
Issue number	52
Online published	27 Oct 2022
DOIs	https://doi.org/10.1002/anie.202203553
Publication status	Published - 23 Dec 2022

Funding

We thank Dr. Xiaona Chen and Prof. Huating Wang for their assistance and discussion. Research Grants Council of the Hong Kong SAR, China Projects [CityU 11100222, CityU 11100421, CityU 11101519, CityU 11100218, N_CityU110/17]; National Natural Science Foundation of China Project [32222089]; Croucher Foundation Project [9509003]; State Key Laboratory of Marine Pollution Director Discretionary Fund; City University of Hong Kong projects [7005503, 9667222, 9680261] to C.K.K. The National Natural Science Foundation of China (No. 21977124, 81973184) to the Tan laboratory. CUHK Direct Grant [4053486]; Hong Kong Research Grants Council Area of Excellence Scheme [AoE/M-403/16]; the Innovation and Technology Commission, Hong Kong SAR (State Key Laboratory of Agrobiotechnology, CUHK) to T.F.C.; Hong Kong Ph.D. Fellowship Scheme to E.Y.C.C.; The grants from Tung Biomedical Sciences Center to J.S.

Research Keywords

ADAR
DHX36
Gene Expression
RNA
G-Quadruplex
Structure-Function Relationship

Publisher's Copyright Statement

COPYRIGHT TERMS OF DEPOSITED POSTPRINT FILE: This is the peer reviewed version of the following article: Lyu, K., Chen, S-B., Chow, E. Y-C., Zhao, H., Yuan, J-H., Cai, M., Shi, J., Chan, T-F., Tan, J-H., & Kwok, C. K. (2022). An RNA G-Quadruplex Structure within the ADAR 5’UTR Interacts with DHX36 Helicase to Regulate Translation. Angewandte Chemie (International Edition), 61(52), [e202203553], which has been published in final form at https://doi.org/10.1002/anie.202203553.
This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

RGC Funding Information

RGC-funded

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2 Active
3 Finished

GRF: Evolving New L-RNA Aptamers and Developing L-RNA aptamer-peptide Conjugates to Control G-quadruplex Structure-associated Gene Activity
KWOK, C. K. (Principal Investigator / Project Coordinator)
1/01/23 → …
Project: Research
GRF: Developing Novel L-RNA Aptamer to Inhibit Telomerase Activity and Regulate G-Quadruplex-Mediated Gene Expression
KWOK, C. K. (Principal Investigator / Project Coordinator)
1/01/22 → …
Project: Research
GRF: Mapping and Targeting of RNA G-quadruplex Structures in the Human Non-coding Transcriptome
KWOK, C. K. (Principal Investigator / Project Coordinator), Chan, T. F. (Co-Investigator) & TANNER, J. A. (Co-Investigator)
1/01/20 → 7/12/23
Project: Research

Cite this

@article{ae4cff3ad7464302a8aff712152ae004,

title = "An RNA G-Quadruplex Structure within the ADAR 5{\textquoteright}UTR Interacts with DHX36 Helicase to Regulate Translation",

abstract = "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.",

keywords = "ADAR, DHX36, Gene Expression, RNA, G-Quadruplex, Structure-Function Relationship",

author = "Kaixin Lyu and Shuo-Bin Chen and Chow, {Eugene Yui-Ching} and Haizhou Zhao and Jia-Hao Yuan and Meng Cai and Jiahai Shi and Ting-Fung Chan and Jia-Heng Tan and Kwok, {Chun Kit}",

year = "2022",

month = dec,

day = "23",

doi = "10.1002/anie.202203553",

language = "English",

volume = "61",

journal = "Angewandte Chemie (International Edition)",

issn = "1433-7851",

publisher = "John Wiley & Sons",

number = "52",

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TY - JOUR

T1 - An RNA G-Quadruplex Structure within the ADAR 5’UTR Interacts with DHX36 Helicase to Regulate Translation

AU - Lyu, Kaixin

AU - Chen, Shuo-Bin

AU - Chow, Eugene Yui-Ching

AU - Zhao, Haizhou

AU - Yuan, Jia-Hao

AU - Cai, Meng

AU - Shi, Jiahai

AU - Chan, Ting-Fung

AU - Tan, Jia-Heng

AU - Kwok, Chun Kit

PY - 2022/12/23

Y1 - 2022/12/23

N2 - 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.

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.

KW - ADAR

KW - DHX36

KW - Gene Expression

KW - RNA

KW - G-Quadruplex

KW - Structure-Function Relationship

U2 - 10.1002/anie.202203553

DO - 10.1002/anie.202203553

M3 - RGC 21 - Publication in refereed journal

SN - 1433-7851

VL - 61

JO - Angewandte Chemie (International Edition)

JF - Angewandte Chemie (International Edition)

IS - 52

M1 - e202203553

ER -

An RNA G-Quadruplex Structure within the ADAR 5’UTR Interacts with DHX36 Helicase to Regulate Translation

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

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Permanent Link

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Projects

GRF: Evolving New L-RNA Aptamers and Developing L-RNA aptamer-peptide Conjugates to Control G-quadruplex Structure-associated Gene Activity

GRF: Developing Novel L-RNA Aptamer to Inhibit Telomerase Activity and Regulate G-Quadruplex-Mediated Gene Expression

GRF: Mapping and Targeting of RNA G-quadruplex Structures in the Human Non-coding Transcriptome

Cite this