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.
Bibliographical noteFunding 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.
© 2021, The Author(s).
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)