Genetic analysis of loop sequences in the let-7 gene family reveal a relationship between loop evolution and multiple isomiRs.

Tingming Liang,Chang Liu,Li Guo,Chen Yang,Ping Li,John J Rossi

doi:10.1371/journal.pone.0113042

Tingming Liang, Chang Liu + Show 4 more

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https://doi.org/10.1371/journal.pone.0113042

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Journal: PloS one	Publication Date: Nov 14, 2014
Citations: 6	License type: CC BY 4.0

Affiliation: Nanjing Normal University, Nanjing Medical University

Abstract

While mature miRNAs have been widely studied, the terminal loop sequences are rarely examined despite regulating both primary and mature miRNA functions. Herein, we attempted to understand the evolutionary pattern of loop sequences by analyzing loops in the let-7 gene family. Compared to the stable miRNA length distributions seen in most metazoans, higher metazoan species exhibit a longer length distribution. Examination of these loop sequence length distributions, in addition to phylogenetic tree construction, implicated loop sequences as the main evolutionary drivers in miRNA genes. Moreover, loops from relevant clustered miRNA gene families showed varying length distributions and higher levels of nucleotide divergence, even between homologous pre-miRNA loops. Furthermore, we found that specific nucleotides were dominantly distributed in the 5′ and 3′ terminal loop ends, which may contribute to the relatively precise cleavage that leads to a stable isomiR expression profile. Overall, this study provides further insight into miRNA processing and maturation and further enriches our understanding of miRNA biogenesis.

Highlights

MicroRNAs, a class of small non-coding RNA, are widely studied as crucial regulatory molecules able to modulate broad regulatory networks at the post-transcriptional levels [1,2]. miRNA is generated from primary miRNA and precursor miRNA in animals [3], with the premiRNA presenting a stable stem-loop structure
Both of the two arm products, miR-#-5p and miR-#-3p, have been reported to form mature and functional miRNAs [4,5,6,7,8], with the loop sequences connecting miR-#-5p and miR-#-3p in the stem-loop structure typically degraded during miRNA biogenesis
Phylogenetic tree construction showed that the pre-miRNA multicopy loop sequences may be divided into two clusters based on loop and pre-miRNA sequences, with distribution differences noted (Figure S1 in File S1)

Summary

Introduction

MicroRNAs (miRNAs), a class of small non-coding RNA, are widely studied as crucial regulatory molecules able to modulate broad regulatory networks at the post-transcriptional levels [1,2]. miRNA is generated from primary miRNA (pri-miRNA) and precursor miRNA (pre-miRNA) in animals [3], with the premiRNA presenting a stable stem-loop structure. MiRNA is generated from primary miRNA (pri-miRNA) and precursor miRNA (pre-miRNA) in animals [3], with the premiRNA presenting a stable stem-loop structure Both of the two arm products, miR-#-5p and miR-#-3p, have been reported to form mature and functional miRNAs [4,5,6,7,8], with the loop sequences connecting miR-#-5p and miR-#-3p in the stem-loop structure typically degraded during miRNA biogenesis. Most studies have focused on the functional and regulatory roles of miRNAs during miRNA-mRNA recognition as it relates to expression or translational repression. Both pri-miRNA and pre-miRNA may contribute to the regulatory process [9]. The loop nucleotides may tune and alter miRNA activity, controlling the processing precision during the miRNA maturation process [9]

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Conclusion