The Stress-Responding miR-132-3p Shows Evolutionarily Conserved Pathway Interactions

MicroRNAs (miRNAs) are small non-coding RNA chains that can each interact with the 3′-untranslated region of multiple target transcripts in various organisms, humans included. MiRNAs tune entire biological pathways, spanning stress reactions, by regulating the stability and/or translation of their targets. MiRNA genes are often subject to co-evolutionary changes together with their target transcripts, which may be reflected by differences between paralog mouse and primate miRNA/mRNA pairs. However, whether such evolution occurred in stress-related miRNAs remained largely unknown. Here, we report that the stress-induced evolutionarily conserved miR-132-3p, its target transcripts and its regulated pathways provide an intriguing example to exceptionally robust conservation. Mice and human miR-132-3p share six experimentally validated targets and 18 predicted targets with a common miRNA response element. Enrichment analysis and mining in-house and web-available experimental data identified co-regulation by miR-132 in mice and humans of stress-related, inflammatory, metabolic, and neuronal growth pathways. Our findings demonstrate pan-mammalian preservation of miR-132′s neuronal roles, and call for further exploring the corresponding stress-related implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10571-017-0515-z) contains supplementary material, which is available to authorized users.