PSF蛋白和VL30 RNA在可逆基因调控中的作用。
Roles of PSF protein and VL30 RNA in reversible gene regulation.
作者信息
Song Xu, Sun Ying, Garen Alan
机构信息
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
出版信息
Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12189-93. doi: 10.1073/pnas.0505179102. Epub 2005 Aug 3.
Abstract
The mammalian protein PSF contains a DNA-binding domain (DBD) that coordinately represses multiple oncogenic genes in human cell lines, indicating a role for PSF as a human tumor-suppressor protein. PSF also contains two RNA-binding domains (RBD) that form a complex with a noncoding VL30 retroelement RNA, releasing PSF from a gene and reversing repression. Thus, the DBD and RBD in PSF are linked by a mechanism of reversible gene regulation involving a noncoding RNA. This mechanism also could apply to other regulatory proteins that contain both DBD and RBD. The mouse genome has multiple copies of VL30 retroelements that are developmentally regulated, and mouse cells contain VL30 RNAs that have normal and pathological roles in gene regulation. Human chromosome 11 has a VL30 retroelement, and a VL30 EST was identified in human blastocyst cells, indicating that the PSF-VL30 RNA regulatory mechanism also could function in human cells.
摘要
哺乳动物蛋白PSF含有一个DNA结合结构域（DBD），该结构域可协同抑制人类细胞系中的多个致癌基因，这表明PSF作为一种人类肿瘤抑制蛋白发挥作用。PSF还含有两个RNA结合结构域（RBD），它们与一种非编码VL30逆转录元件RNA形成复合物，使PSF从一个基因上释放出来并解除抑制。因此，PSF中的DBD和RBD通过一种涉及非编码RNA的可逆基因调控机制相联系。这种机制也可能适用于其他同时含有DBD和RBD的调节蛋白。小鼠基因组中有多个发育受调控的VL30逆转录元件拷贝，小鼠细胞含有在基因调控中具有正常和病理作用的VL30 RNA。人类11号染色体有一个VL30逆转录元件，并且在人类囊胚细胞中鉴定出一个VL30 EST，这表明PSF-VL30 RNA调控机制也可能在人类细胞中发挥作用。
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