Competition of PTB with TIA proteins for binding to a U-rich cis-element determines tissue-specific splicing of the myosin phosphatase targeting subunit 1.
A considerable amount of smooth muscle phenotypic diversity is generated by tissue-specific and developmentally regulated splicing of alternative exons. The control mechanisms are unknown. We are using a myosin phosphatase targeting subunit-1 (MYPT1) alternative exon as a model to investigate this question. In the present study, we show that the RNA binding proteins TIA and PTB function as antagonistic enhancers and suppressors of splicing of the alternative exon, respectively. Each functions through a single U-rich element, containing two UCUU motifs, just downstream of the alternative exon 5' splice site. Tissue-specific down-regulation of TIA protein in the perinatal period allows PTB to bind to the U-rich element and suppress splicing of the alternative exon as the visceral smooth muscle acquires the fast-phasic smooth muscle contractile phenotype. This provides a novel role for PTB in the tissue-specific regulation of splicing of alternative exons during the generation of smooth muscle phenotypic diversity.
Shukla
Supriya
S
Department of Medicine (Cardiology), Case Western Reserve University School of Medicine, BRB 422, Cleveland, OH 44106-4958, USA.
Del Gatto-Konczak
Fabienne
F
Breathnach
Richard
R
Fisher
Steven A
SA
D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D005091:Exons / Q000502:physiology*; D005895:Gizzard, Avian / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology; D043263:Myosin-Light-Chain Phosphatase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D039102:Poly(A)-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D054645:Protein Phosphatase 1; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D000074019:T-Cell Intracellular Antigen-1
D002352:Carrier Proteins; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D038941:Polypyrimidine Tract-Binding Protein; D010749:Phosphoprotein Phosphatases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human