Mechanisms of action of cytoplasmic microRNAs. Part 5. MicroRNA-mediated silencing caused during translation initiation and post-initiation

Abstract

The scientific review considers the mechanisms of action of cytoplasmic microRNAs, namely miRNA-mediated silencing, which is caused during the initiation and post-initiation period of translation. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. It is known that miRNA-mediated silencing caused during translation initiation occurs due to Argonaute proteins, which compete with cap-binding proteins and the eukaryotic translation initiation factor eIF4E during interaction with the 5’cap structure of mRNA. In cap-dependent translation, the eukaryotic initiation factor eIF4E recognizes the 5’cap and promotes the recruitment of other initiation factors, in particular eIF4G, to assemble the translation initiation complex. Also, the eIF4G factor interacts with some PABP proteins, which leads to the formation of a closed loop of mRNA, determining the recruitment of the ribosome. It is stated that in the post-initiation period of translation, microRNAs can: 1) terminate translation, preventing the attachment or promoting the dissociation of ribosome subunits; 2) induce mRNA degradation during the elongation period or 3) activate protein degradation and sequestration. The authors state that microRNAs can directly or indirectly inhibit the functioning of ribosomes, disrupting the formation of a competent 80S ribosome, or preventing the attachment of ribosome subunits to mRNA, or its promotion along the mRNA, or promoting the dissociation of ribosome subunits. AGO2 protein plays a leading role in the development of silencing caused by disruption of the association of ribosomal subunits. The authors showed that the miRNA-mRNA-target complex migrates to lighter polysomes than mRNA that is not associated with miRNA. The miRISC complex with mRNA and ribosomes can recruit proteolytic enzymes that degrade the nascent polypeptide chain. Thus, miRNA-mediated silencing can be induced during the initiation and post-initiation periods of translation.