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bioRxiv · 10.1101/2023.02.24.529967

Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition

Mercuri, R. L. V.·Conceicao, H. B.·Guardia, G. D. A.·Goldstein, G.·Vibranovski, M. D.·Hinske, L. C.·Galante, P. A. F.
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Abstract

BackgroundReverse transcribed gene copies, or retrocopies, have emerged as a major source of evolutionary novelties. MicroRNAs (miRNAs) are small, highly conserved RNAs molecules among species that serve as key post-transcriptional regulators of gene expression. The birth and subsequent evolution of miRNAs have been addressed, but not fully. ResultsIn this study, we carried out a comprehensive investigation of miRNAs origination through retroduplicated mRNA sequences (retrocopies). We identified 17 retroduplicated miRNAs (retro-miRs) that emerged from mRNAs retrocopies. Four of these retro-miRs had de novo origination within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and were duplicated along with their host mRNAs. We found that retro-miRs are primates specific, including 5 retro-miRs conserved among all primates and two human-specific retro-miRs. All of the retro-miRs were expressed and had predicted and experimentally validated target genes, with the exception of miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes, such as metabolic processes, cell signaling and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs have a potential oncogenic role in cancer, targeting key cancer genes and being overexpressed in several cancer types, including Liver Hepatocellular Carcinoma and Stomach Adenocarcinoma. ConclusionOur findings demonstrate that mRNAs retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play roles in cancer.

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Mercuri, R. L. V., Conceicao, H. B., Guardia, G. D. A., Goldstein, G., Vibranovski, M. D., Hinske, L. C., Galante, P. A. F.. 2023-02-25. Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition. https://doi.org/10.1101/2023.02.24.529967

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