Genetic Analysis of Loop Sequences in the Let-7 Gene Family Reveal a Relationship between Loop Evolution and Multiple IsomiRs |
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| Authors: | Tingming Liang Chen Yang Ping Li Chang Liu Li Guo |
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| Affiliation: | 1. Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.; 2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.; Beckman Research Institute of the City of Hope, United States of America, |
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| 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. |
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