Genetic analysis of loop sequences in the let-7 gene family reveal a relationship between loop evolution and multiple isomiRs.
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.
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.
Tingming
T
Liang
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.
Chen
C
Yang
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.
Ping
P
Li
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.
Chang
C
Liu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Li
L
Guo
D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D006801:Humans; D035683:MicroRNAs / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D010802:Phylogeny
D035683:MicroRNAs