Network Regulation of microRNA Biogenesis and Target Interaction

Shintaro Komatsu; Hiroki Kitai; Hiroshi I Suzuki

doi:10.3390/cells12020306

Network Regulation of microRNA Biogenesis and Target Interaction

Cells. 2023 Jan 13;12(2):306. doi: 10.3390/cells12020306.

Authors

Shintaro Komatsu^{1

2}, Hiroki Kitai^{2

3}, Hiroshi I Suzuki^{1

4

5}

Affiliations

¹ Division of Molecular Oncology, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
² Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
³ Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
⁴ Institute for Glyco-Core Research (iGCORE), Nagoya University, Nagoya 464-8601, Japan.
⁵ Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu 501-1193, Japan.

Abstract

MicroRNAs (miRNAs) are versatile, post-transcriptional regulators of gene expression. Canonical miRNAs are generated through the two-step DROSHA- and DICER-mediated processing of primary miRNA (pri-miRNA) transcripts with optimal or suboptimal features for DROSHA and DICER cleavage and loading into Argonaute (AGO) proteins, whereas multiple hairpin-structured RNAs are encoded in the genome and could be a source of non-canonical miRNAs. Recent advances in miRNA biogenesis research have revealed details of the structural basis of miRNA processing and cluster assistance mechanisms that facilitate the processing of suboptimal hairpins encoded together with optimal hairpins in polycistronic pri-miRNAs. In addition, a deeper investigation of miRNA-target interaction has provided insights into the complexity of target recognition with distinct outcomes, including target-mediated miRNA degradation (TDMD) and cooperation in target regulation by multiple miRNAs. Therefore, the coordinated or network regulation of both miRNA biogenesis and miRNA-target interaction is prevalent in miRNA biology. Alongside recent advances in the mechanistic investigation of miRNA functions, this review summarizes recent findings regarding the ordered regulation of miRNA biogenesis and miRNA-target interaction.

Keywords: biogenesis; cotargeting; microRNA; target-mediated miRNA degradation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

MicroRNAs* / metabolism
RNA Processing, Post-Transcriptional

Substances

MicroRNAs

Grants and funding

This work was supported in part by JSPS KAKENHI (19K24694 (H.I.S.)), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (H.I.S.), a Grant for Basic Science Research Projects from the Sumitomo Foundation (H.I.S.), the Mitsubishi Foundation (H.I.S.), the Daiichi Sankyo Foundation of Life Science (H.I.S.), the Uehara Memorial Foundation (H.I.S.), and the Takeda Science Foundation (H.I.S.).