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Functional characterization of putative miRNAlike sequences encoded in the HIV genome
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Resumo(s)
MicroRNAs (miRNAs) are small non-coding RNAs with approximately 19–24 nucleotides long, that
play a critical role in the regulation of many viral and host protein-coding genes. These small RNAs are
encoded by cellular or viral genomes, however, although DNA viruses have been found to produce
miRNAs of similar size to eukaryotic miRNAs, it has been generally assumed that RNA viruses do not
encode miRNAs, based on the notion that the generation of canonical miRNAs from a pre-miRNA
hairpin would result in useless cleavage of the viral genome and transcripts.
HIV retroviruses (HIV-1 and HIV-2) are RNA viruses that have been intensively studied since HIV1 infections constitute one of the biggest health issues of the last decades. Nevertheless, the existence of
HIV-1 encoded miRNAs is still up for debate, while the existence of HIV-2 encoded miRNAs has never
been investigated.
Previous work from our lab using a high-quality dataset of small RNAs from naïve CD4+ T cells
infected with either HIV-1 or HIV-2 detected three candidate molecules, two encoded by the former and
one from the later viral genome that display typical features of authentic miRNAs. With this project, we
aim to experimentally validate the putative HIV-1 and HIV-2 encoded miRNAs as bonafide miRNAs,
dissect the mechanism used by HIV to produce them, and investigate the functional impact of these
molecules in host and viral gene expression. Our results show that both HIV-1 and HIV-2 can encode
strong miRNA candidates that require a hairpin secondary structure to be expressed. Moreover, the
knock-down of Dicer lead to a decrease in the accumulation of mature putative miRNAs for two of our
three candidates, suggesting that they are derived from Dicer-dependent processing, rather than being
merely RNA degradation products. Regarding the functional impact of these miRNAs, several viral and
host targets were predicted. Importantly, the list of predicted targets for all three molecules seems to be
enriched in biological processes, molecular functions, and cellular compartments related to the
regulation of viral infection, latency, and cell survival.
Overall, our results were able to support the existence of putative HIV-encoded miRNAs and provide
new insights regarding the v-miRNA-dependent regulatory mechanisms linked to the pathobiology of
HIV-1 and HIV-2, warranting future in-depth studies.
Descrição
Tese de mestrado, Biologia Humana e Ambiente, 2022, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
microRNAs v-miRNAs HIV-1 HIV-2 interação vírus-hospedeiro Teses de mestrado - 2022