Addressing functional and evolutionary implications of microRNA variation at the DNA and RNA levels in primates
microRNAs are small non-coding RNAs with crucial roles in gene regulation and whose contribution to animal evolution has been largely demonstrated. In this thesis we explored some functional consequences of microRNA sequence variation and their possible effects in primate evolution. We first evaluat...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/585943 |
| Acceso en línea: | http://hdl.handle.net/10803/585943 |
| Access Level: | acceso abierto |
| Palabra clave: | microRNAs evolution primates great apes RNA editing evolución grandes simios edición del ARN 575 |
| Sumario: | microRNAs are small non-coding RNAs with crucial roles in gene regulation and whose contribution to animal evolution has been largely demonstrated. In this thesis we explored some functional consequences of microRNA sequence variation and their possible effects in primate evolution. We first evaluated microRNA nucleotide variation at the genomic level in great apes. Taking advantage of recently published whole-genome sequencing data from 82 individuals including oragutans, gorillas, bonobos, chimpanzees and humans, we analyzed microRNA sequence conservation patterns, both among and within populations. We observed that the entire microRNA mature region was significantly conserved, suggesting its central role for the microRNA regulatory function. We additionally observed that more conserved microRNAs tend to be older, duplicated, clustered, highly associated with disease and show higher expression levels. Further functional analyses revealed that lineage-specific changes in the microRNA mature sequences and/or in the length of the precursor molecules of mir-299, mir-503, mir-508 and mir-541 altered their expression levels and redirected the spectrum of target genes and regulatory networks, some of them linked to neuronal functions. We secondly investigated microRNA sequence variation generated by RNA editing. Focusing on mir-376a1 we studied the RNA editing patterns among different primate individuals including human placenta and macaque, gorilla, chimpanzee and human brain cortex samples. Although mir-376a1 editing showed high inter-individual variation, it was more frequently detected in brain than in placenta and in one particular site. This highly edited site conferred the highest stability to the hairpin molecule, revealing the important contribution of RNA editing to the stability of the transcripts. In summary, we provide evidence on how DNA and RNA nucleotide changes may drive microRNA diversification and redefine new regulatory functions, which could have importantly contributed to primate phenotypic diversification processes and to the recent evolution of our species. |
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