The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2

@article{Yang2007TheMM,
  title={The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2},
  author={Baofeng Yang and Huixian Lin and Jiening Xiao and Yanjie Lu and Xiaobin Luo and Baoxin Li and Ying Zhang and Chaoqian Xu and Yunlong Bai and Hui-zhen Wang and Guohao Chen and Zhiguo Wang},
  journal={Nature Medicine},
  year={2007},
  volume={13},
  pages={486-491}
}
MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3′-untranslated regions of target mRNAs. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and… 

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References

SHOWING 1-10 OF 24 REFERENCES

MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy

TLDR
It is proposed that microRNAs play an essential regulatory role in the development of cardiac hypertrophy, wherein downregulation of miR-1 is necessary for the relief of growth-related target genes from its repressive influence and induction ofhypertrophy.

The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation

TLDR
The results show that two mature miRNAs, derived from the same miRNA polycistron and transcribed together, can carry out distinct biological functions and suggest a molecular mechanism in which miRN as participate in transcriptional circuits that control skeletal muscle gene expression and embryonic development.

Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis

TLDR
It is found that the miR-1 genes are direct transcriptional targets of muscle differentiation regulators including serum response factor, MyoD and Mef2, and a new algorithm for microRNA target identification that incorporates features of RNA structure and target accessibility is used.

Myogenic factors that regulate expression of muscle-specific microRNAs.

TLDR
This work suggests that induction of these microRNAs is important in regulating the expression of muscle-specific proteins, and demonstrates that the myogenic factors Myogenin and MyoD bind to regions upstream of thesemicroRNAs and are likely to regulate their expression.

Silencing of microRNAs in vivo with ‘antagomirs’

TLDR
It is shown that a novel class of chemically engineered oligonucleotides, termed ‘antagomirs’, are efficient and specific silencers of endogenous miRNA levels in mice and may represent a therapeutic strategy for silencing miRNAs in disease.

A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure

TLDR
Findings reveal an important role for specific miRNAs in the control of hypertrophic growth and chamber remodeling of the heart in response to pathological signaling and point to mi RNAs as potential therapeutic targets in heart disease.

Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis

TLDR
It is concluded that miRNA-mediated regulation has a complexity of cellular outcomes and that miRNAs can be mediators of regulation of cell growth and apoptosis pathways.

Direct injection and expression in vivo of full-length cDNA of the cardiac isoform of alpha-2 macroglobulin induces cardiac hypertrophy in the rat heart

TLDR
The induction of cardiac hypertrophy upon direct injection of the full-length cDNA of the cardiac isoform of α-2 M obtained from hypertrophied rat heart mRNA and cloned in an eukaryotic expression vector was confirmed.