4.6 Article

Antisense noncoding mitochondrial RNA-2 gives rise to miR-4485-3p by Dicer processing in vitro

Journal

BIOLOGICAL RESEARCH
Volume 54, Issue 1, Pages -

Publisher

SOC BIOLGIA CHILE
DOI: 10.1186/s40659-021-00356-0

Keywords

ncRNA; miRNA; Cancer; lncRNA; Dicer; Cloning

Categories

Funding

  1. ANID, Chile [Fondecyt-1140345, AFB-170004]

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The study demonstrates that ASncmtRNA-2 may act as a precursor for miR-4485-3p, with in vitro experiments supporting this hypothesis. The evidence strengthens the application of ASncmtRNA knockdown for cancer therapy, as miR-4485-3p is classified as a tumor suppressor miRNA.
Background The antisense noncoding mitochondrial RNAs (ASncmtRNAs) derive from the mitochondrial 16S gene. Knockdown of these transcripts with chemically-modified antisense oligonucleotides induces proliferative arrest, apoptosis and invasiveness reduction in tumor but not normal cells. One of these transcripts, ASncmtRNA-2, contains the complete and identical sequence of hsa-miR-4485-3p and, upon knockdown of this transcript, there is a strong increase in levels of this miRNA, suggesting ASncmtRNA-2 as a source for miR-4485-3p, which is supported by several evidences from our group and others, in the ex vivo setting. Results Here we show that incubation of in vitro-transcribed ASncmtRNA-2 with recombinant Dicer produces RNA fragments corresponding to hsa-miR-4485-3p, showing that Dicer binds to and processes ASncmtRNA-2, strongly supporting the hypothesis that ASncmtRNA-2 acts as a precursor for miR-4485-3p. Conclusion The in vitro results presented here strengthen the hypothesis that miR-4485-3p is derived from ASncmtRNA-2 by Dicer processing. Since miR-4485-3p is classified as a tumor suppressor miRNA, this evidence strengthens the application of ASncmtRNA knockdown for cancer therapy.

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