Loss of Pinin expression attenuates expression levels of SR family splicing factors and modulates alternative pre-mRNA splicing in vivo

碩士 === 長庚大學 === 基礎醫學研究所 === 94 === Pinin (Pnn) was first identified and characterized as a protein closely associated with mature desmosomes of epithelial cells, and several studies have indicated that Pnn can enhance the intermediate filaments organization and the linkage between intermediate filam...

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Bibliographic Details
Main Authors: Ya-Li Chiu, 邱雅莉
Other Authors: Pin Ouyang
Format: Others
Language:zh-TW
Published: 2006
Online Access:http://ndltd.ncl.edu.tw/handle/99083164805654584806
Description
Summary:碩士 === 長庚大學 === 基礎醫學研究所 === 94 === Pinin (Pnn) was first identified and characterized as a protein closely associated with mature desmosomes of epithelial cells, and several studies have indicated that Pnn can enhance the intermediate filaments organization and the linkage between intermediate filaments and desmosone. Pnn is not only found at desmosome(d-form pnn), but also localized in speckled domains of the nuclear( n-form pnn) . In the nucleus Pnn is involved in the pre-mRNA splicing, and regulates mRNA alternative splicing through interaction with members of SR family proteins. To characterize the functional relationship between Pnn and SR proteins, we utilized RNAi in this study to knock-down the endogenous Pnn. We showed that depletion of Pnn expression induces reduced expression of several SR family proteins, including SC-35, SRm300, SRp55, and SRp40, but not that of other nuclear proteins, such as p53, MDM2, and ki67. Additionally, we also demonstrated that depletion of Pnn expression could modulate splice site selection of model reporter minigene in vivo. Our finding is significant in terms of regulation of SR protein cellular concentration because it reveals that Pnn may play a general role in the control of the cellular amount of family SR proteins through downregulation of its own expression, whereby providing us with a better understanding of the cellular mechanism by which Pnn fulfills its biological function.