生物
掷骰子
阿尔戈瑙特
转移RNA
核糖核酸
小RNA
德罗沙
RNA聚合酶Ⅲ
细胞生物学
RNA结合蛋白
小干扰RNA
分子生物学
RNA干扰
遗传学
RNA聚合酶
基因
作者
Daniele Hasler,G. Lehmann,Yasuhiro Murakawa,Filippos Klironomos,Leonhard Jakob,Friedrich A. Grässer,Nikolaus Rajewsky,Markus Landthaler,Gunter Meister
出处
期刊:Molecular Cell
[Elsevier]
日期:2016-06-25
卷期号:63 (1): 110-124
被引量:115
标识
DOI:10.1016/j.molcel.2016.05.026
摘要
The Lupus autoantigen La is an RNA-binding protein that stabilizes RNA polymerase III (Pol III) transcripts and supports RNA folding and has in addition been implicated in the mammalian microRNA (miRNA) pathway. Here, we have analyzed effects of La depletion on Argonaute (Ago)-bound small RNAs in human cells. We find that in the absence of La, distinct tRNA fragments are loaded into Ago proteins. Thus, La functions as gatekeeper ensuring correct tRNA maturation and protecting the miRNA pathway from potentially functional tRNA fragments. However, one specific isoleucin pre-tRNA produces both a functional tRNA and a miRNA even when La is present. We demonstrate that the fully complementary 5′ leader and 3′ trailer of the pre-tRNA-Ile form a double-stranded RNA molecule that has low affinity to La. Instead, Exportin-5 (Xpo5) recognizes it as miRNA precursor and transports it into the cytoplasm for Dicer processing and Ago loading.
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