Molecular mechanisms of RNA interference.

Molecular mechanisms of RNA interference.
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DOI:
10.1146/annurev-biophys-083012-130404
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发表时间:
2013
影响因子:
12.4
通讯作者:
Doudna JA
Doudna JA
中科院分区:
生物学1区
文献类型:
--
作者:
Wilson RC;Doudna JA

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小RNA分子在发育过程中调节真核基因表达,并响应包括病毒感染在内的应激。专门的核糖核酸酶和RNA结合蛋白控制小调节RNA的产生和作用。在Drosha在细胞核中进行初始加工后,pre-miRNA被转运到细胞质中,在细胞质中Dicer切割产生成熟的microRNA(miRNA)和短干扰RNA(siRNA)。这些双链产物与Argonaute蛋白组装,使得一条链被优先选择并用于通过核酸内切切割或翻译抑制来引导互补靶mRNA的序列特异性沉默。Dicer和Argonaute蛋白的分子结构以及RNA结合的复合物为RNA沉默途径的核心机制提供了令人兴奋的见解。
Small RNA molecules regulate eukaryotic gene expression during development and in response to stresses including viral infection. Specialized ribonucleases and RNA binding proteins govern the production and action of small regulatory RNAs. After initial processing in the nucleus by Drosha, pre-miRNAs are transported to the cytoplasm, where Dicer cleavage generates mature microRNAs (miRNAs) and short interfering RNAs (siRNAs). These double-stranded products assemble with Argonaute proteins such that one strand is preferentially selected and used to guide sequence-specific silencing of complementary target mRNAs by endonucleolytic cleavage or translational repression. Molecular structures of Dicer and Argonaute proteins, and RNA-bound complexes, have offered exciting insight into the mechanisms operating at the heart of RNA silencing pathways.
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