Recent insights and novel bioinformatics tools to understand the role of microRNAs binding to 5' untranslated region

Letizia Da Sacco, Andrea Masotti, Letizia Da Sacco, Andrea Masotti

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through the binding of the 3' untranslated region (3'UTR) of specific mRNAs. MiRNAs are post-transcriptional regulators and determine the repression of translation processes or the degradation of mRNA targets. Recently, another kind of miRNA-mediated regulation of translation (repression or activation) involving the binding of miRNA to the 5'UTR of target gene has been reported. The possible interactions and the mechanism of action have been reported in many works that we reviewed here. Moreover, we discussed also the available bioinformatics tools for predicting the miRNA binding sites in the 5'UTR and public databases collecting this information.

Figures

Figure 1
Figure 1
Schematic representation of cap-dependent translation. The initiation factor eIF4E recognizes the 5′cap and promotes the recruitment of eIF4G generating the initiation complex. Ribosome is recruited at the 5′ end of mRNA, and translation takes place once the scanning of 5′UTR is complete and the AUG codon is reached. (Adapted from [11]).
Figure 2
Figure 2
Schematic representation of miRNA-mediated inhibition of translation. The RISC complex loaded with a miRNA interferes with the cap recognition by eIF4F and the recruitment of ribosomal subunits 60S and 40S, preventing the ribosome complex formation and leading to inhibition of translation initiation. (Adapted from [11]).
Figure 3
Figure 3
Schematic representation of miRNA-mediated post-initiation inhibition. Among the various mechanistic hypotheses, the miRISC complex may inhibit the ribosomal elongation, induce ribosome drop-off or facilitate the degradation of nascent polypeptides. (Adapted from [11]).
Figure 4
Figure 4
Schematic representation of miRNA-mediated mRNA degradation. The AGO2 protein interacts with GW182, whereas the enzymes DCP1/2 remove the 5′cap. Exonucleases start the deadenylation process, leading to the degradation of the mRNA. (Adapted from [11]).
Figure 5
Figure 5
Liver specific miR-122 stimulates translation of HCV RNA through direct binding to two target sites in the 5′-UTR. (Adapted from [7]).
Figure 6
Figure 6
The binding site of miR-10a has been identified downstream of the regulatory 5′ oligopyrimidine tract (5′TOP) motif of ribosomal proteins (RP) mRNAs, although with an incomplete base pairing between the 5′UTR and the miRNA seed region.

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Source: PubMed

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