Adenosine-to-Inosine Editing of MicroRNA-487b Alters Target Gene Selection After Ischemia and Promotes Neovascularization

Circulation Research
Reginald V C T van der KwastA Yaël Nossent

Abstract

Adenosine-to-inosine editing of microRNAs has the potential to cause a shift in target site selection. 2'-O-ribose-methylation of adenosine residues, however, has been shown to inhibit adenosine-to-inosine editing. To investigate whether angiomiR miR487b is subject to adenosine-to-inosine editing or 2'-O-ribose-methylation during neovascularization. Complementary DNA was prepared from C57BL/6-mice subjected to hindlimb ischemia. Using Sanger sequencing and endonuclease digestion, we identified and validated adenosine-to-inosine editing of the miR487b seed sequence. In the gastrocnemius muscle, pri-miR487b editing increased from 6.7±0.4% before to 11.7±1.6% (P=0.02) 1 day after ischemia. Edited pri-miR487b is processed into a novel microRNA, edited miR487b, which is also upregulated after ischemia. We confirmed editing of miR487b in multiple human primary vascular cell types. Short interfering RNA-mediated knockdown demonstrated that editing is adenosine deaminase acting on RNA 1 and 2 dependent. Using reverse-transcription at low dNTP concentrations followed by quantitative-PCR, we found that the same adenosine residue is methylated in mice and human primary cells. In the murine gastrocnemius, the estimated methylation fraction...Continue Reading

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Citations

Apr 2, 2019·Journal of Cellular and Molecular Medicine·Karin H SimonsPaul H A Quax
Oct 13, 2019·Cardiovascular Research·Anne Yaël Nossent
Oct 26, 2018·Circulation. Genomic and Precision Medicine·Aikaterini Gatsiou, Konstantinos Stellos
Jul 8, 2020·International Journal of Molecular Sciences·Laura ParmaPaul H A Quax
Dec 29, 2019·Cells·Reginald V C T van der KwastA Yaël Nossent
Jul 12, 2020·Cancers·Giulia RomanoPatrick Nana-Sinkam
Oct 23, 2019·Molecular Therapy : the Journal of the American Society of Gene Therapy·Reginald V C T van der KwastA Yaël Nossent
Jan 22, 2019·Molecular Therapy. Nucleic Acids·Angela Downie Ruiz VelascoA Yaël Nossent
Sep 2, 2021·Critical Reviews in Toxicology·Akin Cayir

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