Rapidly Evolving MicroRNAs Retain Their Targets by a Co‐Evolution Mechanism

Abstract

MicroRNAs (miRNAs) are small regulatory molecules with diverse roles in many biological systems. Most studies to date have focused on the function of conserved miRNAs. In contrast, little is known about rapidly evolving miRNAs despite their preponderance in some biological systems, including the reproductive tract. Here, we asked whether rapidly evolving miRNAs have changed their target repertoire in different species or whether they have co‐evolved with their targets to maintain regulation. As a model system to address this question, we used a set of rapidly evolving X‐linked miRNA genes selectively expressed in the testis: the X‐mir1 gene cluster. Using reporter analysis, we identified several targets regulated by both human and mouse X‐miR1 family members despite their having little or no sequences in common. Intriguingly, 3 of the 5 targets we identified with this characteristic encode translation regulatory factors—FMRP, eIF4e and CYFIP1—suggesting that the X‐mir1 cluster has a role in translational regulation in male germ cells. We found that multiple members of the X‐miR1 cluster regulated these targets, suggesting that this miRNA cluster acts as a functional unit. We propose that rapidly evolving miRNAs create a flexible regulatory environment, but at the same time, they retain crucial targets through co‐evolutionary mechanisms to maintain their physiological roles.Study supported by NIH.