The regulatory impact of RNA-binding proteins on microRNA targeting

Sukjun Kim; Soyoung Kim; Hee Ryung Chang; Doyeon Kim; Junehee Park; Narae Son; Joori Park; Minhyuk Yoon; Gwangung Chae; Young Kook Kim; V. Narry Kim; Yoon Ki Kim; Jin Wu Nam; Chanseok Shin; Daehyun Baek

doi:10.1038/s41467-021-25078-5

The regulatory impact of RNA-binding proteins on microRNA targeting

Sukjun Kim, Soyoung Kim, Hee Ryung Chang, Doyeon Kim, Junehee Park, Narae Son, Joori Park, Minhyuk Yoon, Gwangung Chae, Young Kook Kim, V. Narry Kim, Yoon Ki Kim, Jin Wu Nam, Chanseok Shin, Daehyun Baek

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.

Original language	English
Article number	5057
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25078-5
Publication status	Published - 2021 Dec 1

Bibliographical note

Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT, Republic of Korea (NRF-2014M3C9A3063541, NRF-2019M3E5D3073104, NRF-2020R1A2C3007032, and NRF-2020R1A5A1018081), Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (HI15C3224) and the Institute for Basic Science (IBS) from the Ministry of Science and ICT of Korea (IBS-R008-D1) to D.B. This work was also supported by Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ01577601) Rural Development Administration, Republic of Korea and the NRF grant funded by the Ministry of Science and ICT, Republic of Korea (NRF-2021R1A5A1032428) to C.S.

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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10.1038/s41467-021-25078-5

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title = "The regulatory impact of RNA-binding proteins on microRNA targeting",

abstract = "Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.",

author = "Sukjun Kim and Soyoung Kim and Chang, {Hee Ryung} and Doyeon Kim and Junehee Park and Narae Son and Joori Park and Minhyuk Yoon and Gwangung Chae and Kim, {Young Kook} and Kim, {V. Narry} and Kim, {Yoon Ki} and Nam, {Jin Wu} and Chanseok Shin and Daehyun Baek",

note = "Funding Information: This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT, Republic of Korea (NRF-2014M3C9A3063541, NRF-2019M3E5D3073104, NRF-2020R1A2C3007032, and NRF-2020R1A5A1018081), Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (HI15C3224) and the Institute for Basic Science (IBS) from the Ministry of Science and ICT of Korea (IBS-R008-D1) to D.B. This work was also supported by Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ01577601) Rural Development Administration, Republic of Korea and the NRF grant funded by the Ministry of Science and ICT, Republic of Korea (NRF-2021R1A5A1032428) to C.S. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Kim, Sukjun

AU - Kim, Soyoung

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AU - Kim, Doyeon

AU - Park, Junehee

AU - Son, Narae

AU - Park, Joori

AU - Yoon, Minhyuk

AU - Chae, Gwangung

AU - Kim, Young Kook

AU - Kim, V. Narry

AU - Kim, Yoon Ki

AU - Nam, Jin Wu

AU - Shin, Chanseok

AU - Baek, Daehyun

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N2 - Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.

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The regulatory impact of RNA-binding proteins on microRNA targeting

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