Myofibril-Inducing RNA (MIR) is essential for tropomyosinexpression and myofibrillogenesis in axolotl hearts

摘要

The Mexican axolotl, Ambystoma mexicanum, carries the naturally-occurring recessive mutant gene'c' that results in a failure of homozygous (c/c) embryos to form hearts that beat because of anabsence of organized myofibrils. Our previous studies have shown that a noncoding RNA,Myofibril-Inducing RNA (MIR), is capable of promoting myofibrillogenesis and heart beating in themutant (c/c) axolotls. The present study demonstrates that the MIR gene is essential fortropomyosin (TM) expression in axolotl hearts during development. Gene expression studies showthat mRNA expression of various tropomyosin isoforms in untreated mutant hearts and in normalhearts knocked down with double-stranded MIR (dsMIR) are similar to untreated normal.However, at the protein level, selected tropomyosin isoforms are significantly reduced in mutantand dsMIR treated normal hearts. These results suggest that MIR is involved in controlling thetranslation or post-translation of various TM isoforms and subsequently of regulating cardiaccontractility.