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学科主题: 药学
题名:
Exploring Directional Invasion of Serum Nuclease into siRNA Duplexes by Asymmetrical Terminal Modifications
作者: Huang, Ye1; Ma, Yuan1; Guo, Yujia1; Zou, Lang1; Jin, Hongwei1; Zhong, Lijun; Wu, Yun1; Zhang, Lihe1,2; Yang, Zhenjun1
关键词: hydrolases ; nucleases ; RNA ; small interfering RNAs
刊名: CHEMMEDCHEM
发表日期: 2014-09-01
DOI: 10.1002/cmdc.201402115
卷: 9, 期:9, 页:2111-2119
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Medicinal ; Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: MASS-SPECTROMETRY ; RNA INTERFERENCE ; PASSENGER-STRAND ; MAMMALIAN-CELLS ; RIBONUCLEASE-A ; DEGRADATION ; STABILITY ; INHIBITION ; CLEAVAGE ; SEQUENCE
英文摘要:

In this study we demonstrated that ribonuclease A (RNase A) can recognize the thermodynamic asymmetry of siRNA duplexes, similar to other proteins involved in siRNA function such as argonaute 2. RNase A preferentially invades the siRNA duplex through the less stable terminus, i.e., the 3′ terminus of the sense strand. As evidence, only phosphorothioate (PS) modification at the sense strand overhang improved serum stability, whereas PS modification at the antisense strand overhang did not affect stability. Moreover, the improvement in stability caused by modification at the sense strand overhang was found to correlate with the terminal base pair composition of the siRNA. Gel electrophoresis and MALDI-TOF MS analysis indicated that modifications at the sense strand overhang improved the serum stability of siRNAs by inhibiting the directional invasion of RNase A. The blocking effect was not brought about by stabilization of the siRNA duplexes because there was no clear difference between the melting temperatures of siRNAs with PS modifications at each 3′ overhang.

语种: 英语
所属项目编号: 20932001 ; 2009ZX09503 ; 2012AA022501 ; 2012CB720604
项目资助者: National Natural Sciences Foundation of China ; Program of the Ministry of Science and Technology of China
WOS记录号: WOS:000341623300021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54712
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100871, Peoples R China
2.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Huang, Ye,Ma, Yuan,Guo, Yujia,et al. Exploring Directional Invasion of Serum Nuclease into siRNA Duplexes by Asymmetrical Terminal Modifications[J]. CHEMMEDCHEM,2014,9(9):2111-2119.
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