Egulating gene expression through RNA nuclear retention
Egulating gene expression through RNA nuclear retention
复制标题
DOI：
10.1016/j.cell.2005.08.033
复制
发表时间：
2005-10-21
期刊：
影响因子：
64.5
通讯作者：
Spector, DL
中科院分区：
文献类型：
--
作者：
Prasanth, KV;Prasanth, SG;Spector, DL
已经进化出多种机制来调节真核基因组。我们已经鉴定出 CTN-RNA，一种与 8 kb 核保留聚 (A)(+) RNA 相似的小鼠组织特异性 RNA，可调节其蛋白质编码伙伴的水平。 CTN-RNA 通过替代启动子和 Poly(A) 位点从编码蛋白质的小鼠阳离子氨基酸转运蛋白 2 (mCAT2) 基因转录而来。 CTN-RNA 广泛分布在细胞核中，也定位于副斑雀。 CTN-RNA 的 3'UTR 包含腺苷至肌苷编辑元件，参与其核保留。有趣的是，CTN-RNA 的敲除也会下调 mCAT2 mRNA。在压力下，CTN-RNA 被转录后裂解，产生编码蛋白质的 mCAT2 mRNA。我们的研究结果揭示了细胞核在容纳 RNA 分子方面的作用，这些分子并非立即需要产生蛋白质，但在生理应激时迅速需要其细胞质的存在。这种作用机制凸显了核保留的稳定RNA转录本在调节基因表达中的作用的重要范例。
Multiple mechanisms have evolved to regulate the eukaryotic genome. We have identified CTN-RNA, a mouse tissue-specific similar to 8 kb nuclear-retained poly(A)(+) RNA that regulates the level of its protein-coding partner. CTN-RNA is transcribed from the protein-coding mouse cationic amino acid transporter 2 (mCAT2) gene through alternative promoter and poly(A) site usage. CTN-RNA is diffusely distributed in nuclei and is also localized to paraspeckles. The 3'UTR of CTN-RNA contains elements for adenosine-to-inosine editing, involved in its nuclear retention. Interestingly, knockdown of CTN-RNA also downregulates mCAT2 mRNA. Under stress, CTN-RNA is posttranscriptionally cleaved to produce protein-coding mCAT2 mRNA. Our findings reveal a role of the cell nucleus in harboring RNA molecules that are not immediately needed to produce proteins but whose cytoplasmic presence is rapidly required upon physiologic stress. This mechanism of action highlights an important paradigm for the role of a nuclear-retained stable RNA transcript in regulating gene expression.