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

被引:29
|
作者
Fasanaro, Pasquale [1 ]
Romani, Sveva [2 ]
Voellenkle, Christine [3 ]
Maimone, Biagina [1 ]
Capogrossi, Maurizio C. [1 ]
Martelli, Fabio [3 ]
机构
[1] Ist Dermopat Immacolata IRCCS, Rome, Italy
[2] IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
[3] IRCCS Policlin San Donato, Milan, Italy
来源
PLOS ONE | 2012年 / 7卷 / 09期
关键词
ENDOTHELIAL-CELLS; MICRORNA; DIFFERENTIATION; EXPRESSION; IDENTIFICATION; RECOGNITION; REGULATOR; SURVIVAL; BINDING; SITES;
D O I
10.1371/journal.pone.0044651
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:8
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