drosophila muscleblind is involved in troponin t alternative splicing and apoptosis果蝇muscleblind参与肌钙蛋白t可变剪接和细胞凋亡.pdfVIP

Drosophila Muscleblind Is Involved in troponin T Alternative Splicing and Apoptosis 1 1¤ 1 1 ´ Marta Vicente-Crespo , Maya Pascual , Juan M. Fernandez-Costa , Amparo Garcia-Lopez , Lidon 1 1 2 1 Monferrer , M. Eugenia Miranda , Lei Zhou , Ruben D. Artero * 1 Department of Genetics, University of Valencia, Valencia, Spain, 2 Department of Molecular Genetics and Microbiology Member, University of Florida Shands Cancer Center College of Medicine, University of Florida, Gainesville, Florida, United States of America Abstract Background: Muscleblind-like proteins (MBNL) have been involved in a developmental switch in the use of defined cassette exons. Such transition fails in the CTG repeat expansion disease myotonic dystrophy due, in part, to sequestration of MBNL proteins by CUG repeat RNA. Four protein isoforms (MblA-D) are coded by the unique Drosophila muscleblind gene. Methodology/Principal Findings: We used evolutionary, genetic and cell culture approaches to study muscleblind (mbl) function in flies. The evolutionary study showed that the MblC protein isoform was readily conserved from nematods to Drosophila, which suggests that it performs the most ancestral muscleblind functions. Overexpression of MblC in the fly eye precursors led to an externally rough eye morphology. This phenotype was used in a genetic screen to identify five dominant suppressors and 13 dominant enhancers including Drosophila CUG-BP1 homolog aret, exon junction complex components tsunagi and Aly, and pro-apop