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Study On The Evolutionary Pattern And Mechanism Of MicroRNAs And Their Target Sequences Derived From Transposable Elements

Posted on:2015-12-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:S QinFull Text:PDF
GTID:1100330488497676Subject:Zoology
Abstract/Summary:PDF Full Text Request
MicroRNAs (miRNA), a class of small non-coding RNA (approximately 22 nt), are crucial regulators of gene expressions at the post-transcriptional level in eukaryotes. In animal, mature miRNAs usually regulate gene expression by targeting gene 3’-untranslated regions (3’-UTRs). Understanding the origin and evolution of miRNA will help to recognize the functions of miRNAs and take insights into how miRNAs evolved and gained their functions. Transposable elements (TEs) were claimed as an important source of the origin of pre-miRNA. TE is a class of element which is able to mobilize and replicate in the host genomes with the "copy-paste" way or "cut-paste" way. Many microRNAs are derived from TEs, while it’s still not very clear how TEs contributes to the raise of new miRNAs and miRNA-targets. We analyzed the miRNA data of human and fruit fly to uncover the generated and evolutionary patterns of miRNA and their target sites using the bio-informatics methods. Our researches go as follows:First, we identified the miRNAs derived from TEs in human genome. We found a new pattern of miRNA origin that some miRNAs could partly derive from TEs. MiRNAs can be evolved from the head or tail of TEs with their adjacent sequence of genome. Since some TE will lose their sequence features after forming pre-miRNAs, we inferred that there would be more miRNAs derived from TE in human genome than we found. Based on the up-and down-stream sequence of miRNAs and homologies, we detected additional miRNAs derived from TE which hadn’t been detected before. These additional miRNAs increased the proportion of TE derived miRNAs from 20% to 30% in human genome. The analysis of conservation showed that TE derived miRNAs are less conserved than miRNAs derived from other elements.Second, we analyzed the features of repetitive elements (REs) derived target sites in Drosophila melanogaster. The distribution of miRNA target sites is similar to that of REs showed higher similarity and implied that they might have the potential relationship. When we compared density of target sites, binding energy, GC content and matched base of miRNA and target sites between RE derived target sites and non-RE derived target sites, we found that these features of RE derived target sites are usually weaker than that of non-RE derived target sites. It goes against the binding of miRNAs and their targets. When we analyzed conservation of target sites, we found that RE derived miRNA target sites are less conserved than non-RE derived targets.Third, we analyzed the "miRNA-target"’pairs which are both derived from TEs in human genome and identified 207 conserved "miRNA-target" pairs and thousands of unconserved "miRNA-target" pairs from TE derived miRNA and target sites. We proposed three ways via which "miRNA-target" pairs are both derived from TEs and found that TE derived pairs are significant less than non-TE derived "miRNA-target" pairs between human and mouse for conserved targets, while proportion for unconserved targets is similar. To uncover the functions of TE derived "miRNA-target" pairs, we computed the correlations of expression between miRNAs and mRNAs. Some TE derived miRNAs and their TE derived target sites are significant anti-correlation. It implied that these miRNAs and target sites have functional interactions.Last but not least, we developed softwares to identify and analyze TE derived miRNAs which are covered or uncovered by TEs.Our results indicated that TE play an important role during the miRNA origin and evolution. These findings will show a novel perspective for uncovering the patterns and mechanisms of TE derived miRNAs. It provided important theoretical basis for studying the regulatory functions and mechanisms of miRNAs.
Keywords/Search Tags:transposable element, microRNA, target site, origin, evolution
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