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A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression.
Nature Cell Biology ( IF 21.3 ) Pub Date : 2017-08-21 , DOI: 10.1038/ncb3595
Simon Grelet 1 , Laura A Link 1 , Breege Howley 1 , Clémence Obellianne 1 , Viswanathan Palanisamy 2, 3 , Vamsi K Gangaraju 1, 3 , J Alan Diehl 1, 3 , Philip H Howe 1, 3
Affiliation  

The contribution of lncRNAs to tumour progression and the regulatory mechanisms driving their expression are areas of intense investigation. Here, we characterize the binding of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) to a nucleic acid structural element located in exon 12 of PNUTS (also known as PPP1R10) pre-RNA that regulates its alternative splicing. HnRNP E1 release from this structural element, following its silencing, nucleocytoplasmic translocation or in response to TGFβ, allows alternative splicing and generates a non-coding isoform of PNUTS. Functionally the lncRNA-PNUTS serves as a competitive sponge for miR-205 during epithelial-mesenchymal transition (EMT). In mesenchymal breast tumour cells and in breast tumour samples, the expression of lncRNA-PNUTS is elevated and correlates with levels of ZEB mRNAs. Thus, PNUTS is a bifunctional RNA encoding both PNUTS mRNA and lncRNA-PNUTS, each eliciting distinct biological functions. While PNUTS mRNA is ubiquitously expressed, lncRNA-PNUTS appears to be tightly regulated dependent on the status of hnRNP E1 and tumour context.

中文翻译:

对LncRNA剪接开关的调控PNUTS mRNA可介导EMT和肿瘤进展。

lncRNA对肿瘤进展的贡献和驱动其表达的调控机制是深入研究的领域。在这里,我们表征异质核糖核蛋白E1(hnRNP E1)与位于PNUTS(也称为PPP1R10)前RNA外显子12的核酸结构元件的结合,该RNA调节其选择性剪接。HnRNP E1在沉默,核质易位或响应TGFβ后从该结构元件释放,可以进行选择性剪接并生成PNUTS的非编码同工型。在功能上,lncRNA-PNUTS在上皮-间质转化(EMT)期间可作为miR-205的竞争海绵。在间充质乳腺肿瘤细胞和乳腺肿瘤样品中,lncRNA-PNUTS的表达升高,并且与ZEB mRNA的水平相关。因此,PNUTS是编码PNUTS mRNA和lncRNA-PNUTS的双功能RNA,各自引起不同的生物学功能。虽然PNUTS mRNA普遍存在,但lncRNA-PNUTS似乎受到严格调控,具体取决于hnRNP E1的状态和肿瘤情况。
更新日期:2017-09-07
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