RT Journal Article
SR Electronic
T1 Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.24.529967
DO 10.1101/2023.02.24.529967
A1 Mercuri, Rafael L.
A1 Conceição, Helena B.
A1 Guardia, Gabriela D. A.
A1 Goldstein, Gabriel
A1 Vibranovski, Maria D.
A1 Hinske, Ludwig C.
A1 Galante, Pedro A F
YR 2023
UL http://biorxiv.org/content/early/2023/02/25/2023.02.24.529967.abstract
AB Background Reverse 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.Results In 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.Conclusion Our 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.Competing Interest StatementThe authors have declared no competing interest.