Abstract

mir-548 is a larger, poorly conserved primate-specific miRNA gene family. 69 human mir-548 genes located in almost all human chromosomes whose widespread distribution pattern implicates the evolutionary origin from transposable elements. Higher level of nucleotide divergence was detected between these human miRNA genes, which mainly derived from divergence of multicopy pre-miRNAs and homologous miRNA genes. Products of mir-548, miR-548-5p, and miR-548-3p showed inconsistent evolutionary patterns, which partly contributed to larger genetic distances between pre-miRNAs. “Seed shifting” events could be detected among miR-548 sequences due to various 5′ ends. The events led to shift of seed sequences and target mRNAs, even generated to new target mRNAs. Additionally, the phenomenon of miRNA:miRNA interaction in the miRNA gene family was found. The potential interaction between miRNAs may be contributed to dynamic miRNA expression profiles by complementarily binding events to form miRNA:miRNA duplex with 5′-/3′-overhangs. The miRNA gene family had important roles in multiple biological processes, including signaling pathways and some cancers. The potential abundant roles and functional implication further led to the larger and poorly conserved gene family with genetic variation based on transposable elements. The evolutionary pattern of the primate-specific gene family might contribute to dynamic expression profiles and regulatory network.

Highlights

  • MicroRNAs, a distinct class of ∼22 nt singlestranded noncoding endogenous RNAs, play pivotal roles in negatively regulating gene expression by targeting mRNAs with an influence on multiple biological processes in plants and animals, including cell growth, differentiation, and apoptosis [1,2,3]

  • There were 100 miRNA members that were distributed in primates, including Homo sapiens, Pongo pygmaeus, Pan troglodytes, and Macaca mulatta

  • There were 69 members in the gene family, and higher level of nucleotide divergence could be detected between these homologous miRNA genes

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Summary

Introduction

MicroRNAs (miRNAs), a distinct class of ∼22 nt singlestranded noncoding endogenous RNAs, play pivotal roles in negatively regulating gene expression by targeting mRNAs with an influence on multiple biological processes in plants and animals, including cell growth, differentiation, and apoptosis [1,2,3]. The pri-miRNA is converted into premiRNA with a hairpin structure by Drosha [7,8,9]. PremiRNA is translocated to the cytoplasm via exportin-5 [7] where the miRNA:miRNA∗ duplex is released from the hairpin structure by Dicer [10, 11]. Mature miRNA is loaded into RISC (RNA induced silencing complex) to mediate mRNA targeting [12, 13]. Some miRNAs have higher level of sequence similarity and form the miRNA gene family, and even coregulate complex biological processes

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