Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains
IntroductionThe 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 substi...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1544802/full |
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| author | Xudong Wu Tingting Liu |
| author_facet | Xudong Wu Tingting Liu |
| author_sort | Xudong Wu |
| collection | DOAJ |
| description | IntroductionThe 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. It raises the interesting question of how the miRNAs in the late-replication domain cope with the mutation bias caused by RT.MethodsIn this study, we characterized the genomic distribution of pre-miRNAs in relation to DNA replication timing, and identified 362 pre-miRNAs within late-replicating domains (late-miRNAs) and 631 pre-miRNAs within early-replicating domains (early-miRNAs). We comprehensively examined the multiple molecular features including the secondary structural properties, the genomic sequences surrounding the pre-miRNA loci, the Dicer processing motifs, and CAGE tag-based promoters and miRNAs expression profiles. Furthermore, we performed the simulation of miRNA-target regulatory networks to elucidate the co-regulation patterns among late-miRNAs. To advance predictive capabilities, we developed a a support vector machine (SVM) classifier based on RNA-FM embedding, enabling prediction of miRNAs’ replication timing domains.Results and DiscussionOur study 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 the late-miRNAs tend to synergistically regulate the same genes and are involved in small molecule metabolism, immune responses and so on. The comparative analysis of early- and late- miRNAs confirmed that the information of replication timing domains is inherently encoded in miRNAs’ sequence-structure signatures, and suggested that late-replication specific mutation patterns leave direct imprints on miRNA architecture. 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. |
| format | Article |
| id | doaj-art-cfceca69aa0341ebbbbdb3d1062cb816 |
| institution | DOAJ |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-cfceca69aa0341ebbbbdb3d1062cb8162025-08-20T03:16:11ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-06-011610.3389/fgene.2025.15448021544802Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domainsXudong WuTingting LiuIntroductionThe 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. It raises the interesting question of how the miRNAs in the late-replication domain cope with the mutation bias caused by RT.MethodsIn this study, we characterized the genomic distribution of pre-miRNAs in relation to DNA replication timing, and identified 362 pre-miRNAs within late-replicating domains (late-miRNAs) and 631 pre-miRNAs within early-replicating domains (early-miRNAs). We comprehensively examined the multiple molecular features including the secondary structural properties, the genomic sequences surrounding the pre-miRNA loci, the Dicer processing motifs, and CAGE tag-based promoters and miRNAs expression profiles. Furthermore, we performed the simulation of miRNA-target regulatory networks to elucidate the co-regulation patterns among late-miRNAs. To advance predictive capabilities, we developed a a support vector machine (SVM) classifier based on RNA-FM embedding, enabling prediction of miRNAs’ replication timing domains.Results and DiscussionOur study 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 the late-miRNAs tend to synergistically regulate the same genes and are involved in small molecule metabolism, immune responses and so on. The comparative analysis of early- and late- miRNAs confirmed that the information of replication timing domains is inherently encoded in miRNAs’ sequence-structure signatures, and suggested that late-replication specific mutation patterns leave direct imprints on miRNA architecture. 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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1544802/fullmiRNAreplication temporal domainshairpin structuredicer cleavage sitemiRNA promoterspredictive model |
| spellingShingle | Xudong Wu Tingting Liu Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains Frontiers in Genetics miRNA replication temporal domains hairpin structure dicer cleavage site miRNA promoters predictive model |
| title | Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains |
| title_full | Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains |
| title_fullStr | Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains |
| title_full_unstemmed | Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains |
| title_short | Insights into the evolution and regulation of miRNAs from the view of their DNA replication temporal domains |
| title_sort | insights into the evolution and regulation of mirnas from the view of their dna replication temporal domains |
| topic | miRNA replication temporal domains hairpin structure dicer cleavage site miRNA promoters predictive model |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1544802/full |
| work_keys_str_mv | AT xudongwu insightsintotheevolutionandregulationofmirnasfromtheviewoftheirdnareplicationtemporaldomains AT tingtingliu insightsintotheevolutionandregulationofmirnasfromtheviewoftheirdnareplicationtemporaldomains |