ROD1 Is a Seedless Target Gene of Hypoxia-Induced miR-210

Pasquale Fasanaro, Sveva Romani, Christine Voellenkle, Biagina Maimone, Maurizio C. Capogrossi, Fabio Martelli

Research output: Contribution to journalArticlepeer-review

Abstract

Most metazoan microRNA (miRNA) target sites have perfect pairing to the "seed" sequence, a highly conserved region centering on miRNA nucleotides 2-7. Thus, complementarity to this region is a necessary requirement for target prediction algorithms. However, also non-canonical miRNA binding can confer target regulation. Here, we identified a seedless target of miR-210, a master miRNA of the hypoxic response. We analyzed 20 genes that were inversely correlated to miR-210 expression and did not display any complementarity with miR-210 seed sequence. We validated ROD1 (Regulator of Differentiation 1, also named PTBP3, Polypyrimidine Tract Binding protein 3) as a miR-210 seedless transcript enriched in miR-210-containing RNA-induced silencing complexes. ROD1 was not indirectly targeted by a miR-210-induced miRNA. Conversely, we identified a "centered" miR-210 binding site in ROD1 involving 10 consecutive bases in the central portion of miR-210. Reporter assays showed that miR-210 inhibited ROD1 by the direct binding to this sequence, demonstrating that ROD1 is a bona fide seedless target of miR-210. As expected, both ROD1 mRNA and protein were down-modulated upon hypoxia in a miR-210 dependent manner. ROD1 targeting by miR-210 was biologically significant: the rescue of ROD1 inhibition significantly increased hypoxia-induced cell death. These data highlight the importance of ROD1 regulation by miR-210 for cell homeostasis.

Original languageEnglish
Article numbere44651
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 14 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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