Copyright: © 2025 by the authors. Licensee: Pirogov University.
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REVIEW

miRNA biogenesis and functioning: 30 years since their discovery

Pisklova MV1, Baulina NM1,2, Matveeva NA1,2, Favorova OO1,2
About authors

1 Chazov National Medical Research Center of Cardiology, Moscow, Russia

2 Pirogov Russian National Research Medical University

Correspondence should be addressed: Maria V. Pisklova
Akademika Chazova, 15А, Moscow, 121552, Russia; ur.liam@airam_avolksip

About paper

Funding: the study was conducted within the framework of the State Assignment of the Chazov National Medical Research Center of Cardiology (No. 124020200013-3).

Author contribution: Pisklova MV — literature data acquisition, analysis and systematization, planning and writing the manuscript draft, selecting drawings; Baulina NM, Favorova OO — planning, manuscript structuring, editing; Matveeva NA — literature data analysis and systematization, manuscript writing.

Received: 2024-11-24 Accepted: 2024-12-20 Published online: 2025-01-28
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Fig. 1. Canonical miRNA biogenesis and generation of the functionally active miRISC complex. AAAAn — poly(A) tails at the 3' ends of the mRNA and miRNA molecules; DGCR8 — DiGeorge syndrome critical region 8; Dicer, Drosha — RNase III family endoribonucleases; miRISC — RNA-induced silencing complex bound to the miRNA strand; Ran — Ras-related nuclear protein (GTP-binding nuclear protein); RISC — RNA-induced silencing complex; XPO5 — exportin-5; pre-miRNA — miRNA precursor. The 5' cap is marked with gray circle in the primary miRNA image
Fig. 2. Reported mechanisms underlying miRNA-mediated silencing. А. Inhibition of the target mRNA “closed-loop” formation. Under exposure to the RISC complex, PABPC dissociates from the target mRNA poly(A) tail, making it impossible to interact with eIF4G and preventing formation of the “closed-loop” essential for initiation of mRNA translation. B. Target mRNA decay (on the left) and inhibition of mRNA translation initiation through prevention of the eukaryotic translation initiation factor 4F complex assembly (on the right). Target mRNA is marked with black line; the GW182 protein representing a scaffold for proteins CCR4-NOT and PAN2-PAN3 is marked with yellow line; the guide strand of miRNA being part of the miRISC complex is marked with light-blue line. Gray arrows point to engagement of the CCR4-NOT complex by the AGO proteins with subsequent recruitment of the DCP1 and DCP2 decapping proteins by the CCR4-NOT complex. Modified from [17]