Liang Tingming, Yang Chen, Li Ping, Liu Chang, Guo Li
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
PLoS One. 2014 Nov 14;9(11):e113042. doi: 10.1371/journal.pone.0113042. eCollection 2014.
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.
虽然成熟的微小RNA（miRNA）已得到广泛研究，但尽管末端环序列对初级和成熟miRNA的功能均有调控作用，却很少被研究。在此，我们试图通过分析let-7基因家族中的环来了解环序列的进化模式。与大多数后生动物中稳定的miRNA长度分布不同，高等后生动物物种表现出更长的长度分布。除了构建系统发育树外，对这些环序列长度分布的研究表明，环序列是miRNA基因的主要进化驱动因素。此外，相关成簇miRNA基因家族的环显示出不同的长度分布和更高水平的核苷酸差异，即使在同源前体miRNA环之间也是如此。此外，我们发现特定核苷酸主要分布在5'和3'末端环的末端，这可能有助于相对精确的切割，从而导致稳定的异源miR表达谱。总体而言，本研究为miRNA的加工和成熟提供了进一步的见解，并进一步丰富了我们对miRNA生物发生的理解。
