Computer analysis shows differences between mitochondrial miRNAs and other miRNAs

TL;DR

This paper shows that mitochondrial miRNAs (mitomiRs) have unique features compared to other miRNAs, which could help explain their role in mitochondrial function and disease.

Contribution

The study identifies for the first time key distinguishing features of mitomiRs using a Random Forest classification approach.

Findings

MitomiRs are evolutionarily older than other miRNAs, as indicated by a lower phylostratigraphic age index.

MitomiRs have more targets and disease associations, particularly those related to mitochondria.

MitomiRs are more likely to be classified as 'circulating' miRNAs.

Abstract

A subclass of miRNAs with as yet unknown specific functions is mitomiRs – mitochondrial miRNAs that are mainly derived from nuclear DNA and are imported into mitochondria; moreover, changes in the expression levels of mitomiRs are associated with some diseases. To identify the most pronounced characteristics of mitochondrial miRNAs that distinguish them from other miRNAs, we classified mitomiR sequences using the Random Forest algorithm. The analysis revealed, for the first time, a significant difference between mitomiRs and other microRNAs by the following criteria (in descending order of importance in the classification): mitomiRs are evolutionarily older (have a lower phylostratigraphic age index, PAI); have more targets and disease associations, including mitochondrial ones (two-sided Fisher’s exact test, average p-values 1.82 × 10–89/1.13 × 10–96 for all mRNA/diseases and 6.01 × 10–22/1.09 × 10–9 for mitochondria, respectively); and are in the class of “circulating” miRNAs (average p- value 1.20 × 10–56). The identified differences between mitomiRs and other miRNAs may help uncover the mode of miRNA delivery into mitochondria, indicate the evolutionary conservation and importance of mitomiRs in the regulation of mitochondrial function and metabolism, and generally show that mitomiRs are not randomly encountered miRNAs. Information on 1,312 experimentally validated mitomiR sequences for three organisms (Homo sapiens, Mus musculus and Rattus norvegicus) is collected in the mitomiRdb database (https://mitomiRdb.org).Key words: mitomiR; mitochondria; miRNA; evolution; database.

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