@article{2af73da2c6b6457a991318471ede597b,
title = "ASF/SF2-regulated CaMKIIδ alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle",
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 Ca2+/calmodulin-dependent kinase IIδ (CaMKIIδ) transcript. This failure results in mistargeting of the kinase to sarcolemmal membranes, causing severe excitation-contraction 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 CaMKIIδ alternative splicing to functional remodeling in developing heart.",
author = "Xiangdong Xu and Dongmei Yang and Ding, {Jian Hua} and Wang Wang and Chu, {Pao Hsien} and Dalton, {Nancy D.} and Wang, {Huan You} and Bermingham, {John R.} and Zhen Ye and Forrest Liu and Rosenfeld, {Michael G.} and Manley, {James L.} and John Ross and Ju Chen and Xiao, {Rui Ping} and Heping Cheng and Fu, {Xiang Dong}",
note = "Funding Information: We are grateful to K. Chien, S. Emr, and C. Zuker for critical comments on the manuscript. We thank N. Varki of the UCSD histology core for tissue preparation and expert evaluation; I. Niesman of the CMM EM core for ultrastructural studies; J. Zhao of the UCSD transgenic core for producing transgenic mice; and B. Ziman at NIA, NIH for preparing cardiomyocytes. X.X. and J.-H.D. were the recipients of fellowships from the American Heart Association California Chapter. P.-H.C was supported by grants from NIH of Taiwan. Funding for this work was provided by the U.S. NIH intramural project funds to R.-P.X. and H.C. and by NIH grants to J.C. (RO1 HL66100), J.L.M. (R37 GM48259), and X.-D.F. (RO1 GM49369). ",
year = "2005",
month = jan,
day = "14",
doi = "10.1016/j.cell.2004.11.036",
language = "English",
volume = "120",
pages = "59--72",
journal = "Cell",
issn = "0092-8674",
number = "1",
}