Zdorovʹe Rebenka (Sep 2022)

Mechanisms of action of cytoplasmic miRNAs. Part 4. Recruitment of the DCP1-DCP2 decapping complex. Mechanisms of final mRNA degradation

  • A.E. Abaturov,
  • V.L. Babуch

DOI
https://doi.org/10.22141/2224-0551.17.5.2022.1526
Journal volume & issue
Vol. 17, no. 5
pp. 256 – 261

Abstract

Read online

This scientific review deals with the mechanisms of action of cytoplasmic microRNAs, namely post-transcriptional silencing: recruitment of the DCP1-DCP2 decapping complex and disruption of the interaction of mRNA with ribosomes. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. The authors indicate that the key process that determines both mRNA stability and expression efficiency is the removal of the 5’-terminal cap. Decapping of mRNA is controlled by several direct and indirect regulators. The DCP1-DCP2 complex can be recruited directly to mRNA and indirectly with the help of several decapping enhancers: PAT1 directly interacts with DCP1 and the decapping stimulator; EDC, DDX6. It is known that the protein DCP2 (Nudt20) is a representative of the conserved subfamily of Nudix hydrolases, which catalyze the hydrolysis of small nucleotide substrates. It is presented that the DCP1 protein is a small molecule that contains the EVH1 (enabled/vasodilator-stimula­ted phosphoprotein homology 1) domain, which usually acts as a protein-protein interaction module, and a C-terminal trimerization domain. It is known that the DCP1-DCP2 complex exists in an open and closed conformation, with the closed conformation having catalytic activity. DCP2 protein and its enhancer and cofactor partners accumulate in P-bodies. The authors indicate that in P-bodies, 5’-monophosphorylated mRNA is finally cleaved under the action of 5’-3’-exoribonuclease XRN1. XRN exoribonucleases are vital enzymes whose gene deletion is accompanied by intraembryonic lethality against the background of various abnormalities in the development of organs and systems. Thus, recruitment of the DCP1-DCP2 decapping complex and disruption of the interaction of mRNA with ribosomes in the cytoplasm of the cell are mechanisms of post-transcriptional silencing. The stability of the mRNA and the efficiency of expression determines the removal of the 5’ end cap. Termination of translation is caused by mRNA. MicroRNA-mediated degradation of this mRNA can be carried out both in the 3’-5’ and 5’-3’ directions of the mo­lecule.

Keywords