The regulatory activity of microRNA☆ species has substantial influence on microRNA and 3′ UTR evolution

被引:402
作者
Okamura, Katsutomo [1 ]
Phillips, Michael D. [1 ]
Tyler, David M. [1 ]
Duan, Hong [1 ]
Chou, Yu-Ting [1 ]
Lai, Eric C. [1 ]
机构
[1] Sloan Kettering Inst, Dept Dev Biol, New York, NY 10065 USA
关键词
D O I
10.1038/nsmb.1409
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
During microRNA (miRNA) biogenesis, one strand of a similar to 21-22-nucleotide RNA duplex is preferentially selected for entry into a silencing complex. The other strand, known as the miRNA* species, has typically been assumed to be a carrier strand. Here we show that, although Drosophila melanogaster miRNA* species are less abundant than their partners, they are often present at physiologically relevant levels and can associate with Argonaute proteins. Comparative genomic analyses revealed that > 40% of miRNA* sequences resist nucleotide divergence across Drosophilid evolution, and at least half of these well-conserved miRNA* species select for conserved 3' untranslated region seed matches well above background noise. Finally, we validated the inhibitory activity of miRNA* species in both cultured cells and transgenic animals. These data broaden the reach of the miRNA regulatory network and suggest an important mechanism that diversifies miRNA function during evolution.
引用
收藏
页码:354 / 363
页数:10
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