Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
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DOI：
10.1101/gad.1158803
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发表时间：
2003-12-15
影响因子：
10.5
通讯作者：
Cullen, BR
中科院分区：
文献类型：
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作者：
Yi, R;Qin, Y;Cullen, BR
microRNA（miRNAs）最初表达为长转录物，在细胞核中加工产生类似于65-nt RNA发夹的中间产物，称为pre-miRNAs，这些中间产物被输出到细胞质中进行进一步加工，产生类似于22-nt miRNAs的成熟产物。在这里，我们证明了人类pre-miRNA核输出和miRNA功能依赖于Exportin-5。Exportin-5可以在体外特异性结合pre-miRNA，但仅在Ran-GTP辅因子存在下。短发夹RNA，用于表达小干扰RNA的人工前体miRNA类似物，也依赖于Exportin-5进行核输出。总之，这些发现定义了miRNA生物发生和功能所需的额外细胞辅因子。
MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield similar to65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, similar to22-nt miRNAs. Here, we demonstrate that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5. Exportin-5 can bind pre-miRNAs specifically in vitro, but only in the presence of the Ran-GTP cofactor. Short hairpin RNAs, artificial pre-miRNA analogs used to express small interfering RNAs, also depend on Exportin-5 for nuclear export. Together, these findings define an additional cellular cofactor required for miRNA biogenesis and function.