Author/Authors :
Wang، Qiu-Wang نويسنده , , Chen، Yun Ju نويسنده , , Xu، Xiangdong نويسنده , , Yang، Dongmei نويسنده , , Ding، Jian-Hua نويسنده , , Chu، Pao-Hsien نويسنده , , Dalton، Nancy D. نويسنده , , Wang، Huan-You نويسنده , , Bermingham، John R. نويسنده , , Ye، Zhen نويسنده , , Liu، Forrest نويسنده , , Rosenfeld، Michael G. نويسنده , , Manley، James L. نويسنده , , Ross، John نويسنده , , Xiao، Rui-Ping نويسنده , , Cheng، Heping نويسنده , , Fu، Xiang-Dong نويسنده ,
Abstract :
The transition from juvenile to adult life is accompanied by programmed remodeling in many tissues and organs, which is key for organisms to adapt to the demand of the environment. Here we report a novel regulated alternative splicing program that is crucial for postnatnal heart remodeling in the mouse. We identify the essential splicing factor ASF/SF2 as a key component of the program, regulating a restricted set of tissue-specific alternative splicing events during heart remodeling. Cardiomyocytes deficient in ASF/SF2 display an unexpected hypercontraction phenotype due to a defect in postnatal splicing switch of the Ca^2+/calmodulin-dependent kinase IIo (CaMKIIo) transcript. This failure results in mistargeting of the kinase to sarcolemmal membranes, causing severe excitationcontraction coupling defects. Our results validate ASF/SF2 as a fundamental splicing regulator in the reprogramming pathway and reveal the central contribution of ASF/SF2-regulated CaMKIIo alternative splicing to functional remodeling in developing heart.
Keywords :
DIGLYPHUS ISAEA , Liriomyza trifolii , Biological control , IPM , Greenhouse , Abamectin compatibility
