Differences in silencing of mismatched targets by sliced versus diced siRNAs

Guihua Sun, Jinghan Wang, Yasheng Huang, Christine Wan Yin Yuan, Keqiang Zhang, Shuya Hu, Linling Chen, Ren Jang Lin, Yun Yen, Arthur D. Riggs

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4 引文 斯高帕斯(Scopus)

摘要

It has been reported that the two major types of RNA interference triggers, the classical Dicer-generated small RNAs (siRNAs), which function with all members of the Argonaute (Ago) protein family in mammals, and the Ago2-sliced small RNAs (sli-siRNAs), which function solely through Ago2, have similar potency in target cleavage and repression. Here, we show that sli-siRNAs are generally more potent than siRNAs in silencing mismatched targets. This phenomenon is usually more apparent in targets that have mismatched nucleotides in the 3 supplementary region than in targets with mismatches in the seed region. We demonstrate that Ago2 slicer activity is a major factor contributing to the greater silencing efficiency of sli-siRNA against mismatched targets and that participation of non-slicing Agos in silencing mismatched siRNA targets may dilute the slicing ability of Ago2. The difference in length of the mature guide RNA used in sli-RISCs and si-RISCs may also contribute to the observed difference in knockdown efficiency. Our data suggest that a sli-siRNA guide strand is likely to have substantially stronger off-target effects than a guide strand with the same sequence in a classical siRNA and that Dicer and non-slicing Agos may play pivotal roles in controlling siRNA target specificity.
原文英語
頁(從 - 到)6806-6822
頁數17
期刊Nucleic Acids Research
46
發行號13
DOIs
出版狀態已發佈 - 一月 1 2018

ASJC Scopus subject areas

  • 遺傳學

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