Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains

Xudong Wu^*Tingting Liu

• School of Engineering, Guangzhou College of Technology and Business, Guangzhou, China

The DNA replication of eukaryotes proceeds in a defined temporal sequence known as the replication timing (RT) program. A recent study revealed that the early- and late-replication temporal domains have different DNA mutation patterns and that the late-replicating sequences have a substitution pattern biased towards A and T. This study explored how the miRNAs in the late-replication domain cope with the mutation bias caused by RT, and the results indicated that the late pre-miRNAs maintained their ability to fold into hairpin structures through extending their lengths at both ends under the premise of maintaining a certain GC content of the precursors. The simulation demonstrated that late-miRNAs tend to synergistically regulate the same genes and are involved in small molecule metabolism, immune responses and so on. This study provides insights into the impact of DNA replication timing on miRNA-mediated posttranscriptional regulation and helps us understand the evolutionary mechanism of miRNAs.