RBM20 and RBM24 cooperatively promote the expression of short enh splice variants.
PDZ-LIM protein ENH1 is a scaffold protein for protein kinases and transcriptional regulators. While ENH1 promotes the hypertrophic growth of cardiomyocytes, its short splice variant (ENH3) prevents the hypertrophic growth. The mechanism underlying the alternative splicing of enh mRNA between ENH short and long isoforms has remained unknown. Here, we found that two splicing factors, RNA-binding motif 20 (RBM20) and RNA-binding motif 24 (RBM24) together promoted the expression of short enh splice variants and bound the 5' intronic region of exon 11 containing an in-phase stop codon. In addition, expression of both RBMs is repressed by hypertrophic stimulations. Collectively, our results suggest that, in healthy conditions, RBM20 and RBM24 cooperate to promote the expression of short ENH isoforms.
Graduate School of Bioagricultural Sciences, Nagoya University, Japan.|Japan Society for the Promotion of Science, Tokyo, Japan.
Jumpei
J
Ito
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
Masumi
M
Iijima
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
Nobuo
N
Yoshimoto
Graduate School of Bioagricultural Sciences, Nagoya University, Japan.
Tomoaki
T
Niimi
Graduate School of Bioagricultural Sciences, Nagoya University, Japan.|The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
Shun'ichi
S
Kuroda
Graduate School of Bioagricultural Sciences, Nagoya University, Japan.
Andrés D
AD
Maturana
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D018388:Codon, Terminator / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D007438:Introns / Q000502:physiology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis; D022821:RNA Splice Sites / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D048868:Adaptor Proteins, Signal Transducing; D018388:Codon, Terminator; C102578:Pdlim5 protein, rat; D020033:Protein Isoforms; C573837:RBM20 protein, rat; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins
PDZ-LIM; alternative splicing; scaffold protein