Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL 33431, USA.
J Biomed Sci. 2009 Sep 3;16(1):81. doi: 10.1186/1423-0127-16-81.
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 an absence 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 the mutant (c/c) axolotls. The present study demonstrates that the MIR gene is essential for tropomyosin (TM) expression in axolotl hearts during development. Gene expression studies show that mRNA expression of various tropomyosin isoforms in untreated mutant hearts and in normal hearts knocked down with double-stranded MIR (dsMIR) are similar to untreated normal. However, at the protein level, selected tropomyosin isoforms are significantly reduced in mutant and dsMIR treated normal hearts. These results suggest that MIR is involved in controlling the translation or post-translation of various TM isoforms and subsequently of regulating cardiac contractility.
墨西哥钝口螈,Ambystoma mexicanum,携带自然发生的隐性突变基因“c”,导致纯合子(c/c)胚胎由于缺乏有组织的肌原纤维而无法形成跳动的心脏。我们之前的研究表明,一种非编码 RNA,肌原纤维诱导 RNA(MIR),能够促进突变(c/c)钝口螈的肌原纤维发生和心脏跳动。本研究表明,在发育过程中,MIR 基因对于墨西哥钝口螈心脏中的原肌球蛋白(TM)表达是必需的。基因表达研究表明,未经处理的突变型心脏和用双链 MIR(dsMIR)敲低的正常心脏中的各种原肌球蛋白同工型的 mRNA 表达与未经处理的正常心脏相似。然而,在蛋白质水平上,选定的原肌球蛋白同工型在突变型和 dsMIR 处理的正常心脏中显著减少。这些结果表明,MIR 参与控制各种 TM 同工型的翻译或翻译后过程,并随后调节心脏收缩性。