Key result
RBM20 and RBM24 cooperatively promote short enh splice variant expression via exon 11 intronic binding.
Why the study?
The mechanism underlying the alternative splicing of enh mRNA between ENH short and long isoforms was unknown.
RBM20 and RBM24 cooperatively promote the expression of the anti-hypertrophic short ENH splice variant, providing mechanistic insight into cardiomyocyte hypertrophy.
May modulate cardiac splicing; leaves open whether RBM20/RBM24 targeting alters cardiomyopathy progression.
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.
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Ito et al. (2016) studied this question. RBM20 and RBM24 was evaluated on Expression of short enh splice variants. RBM20 and RBM24 cooperatively promoted the expression of short enh splice variants and bound the 5' intronic region of exon 11 containing an in-phase stop codon.
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