microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart.

By Ning Liu, S. Bezprozvannaya, Andrew H. Williams, X. Qi, J. Richardson, R. Bassel-Duby, E. Olson. Genes & Development, 2008

831 citations recorded by the source corpus.

MicroRNAs (miRNAs) modulate gene expression by inhibiting mRNA translation and promoting mRNA degradation, but little is known of their potential roles in organ formation or function. miR-133a-1 and miR-133a-2 are identical, muscle-specific miRNAs that are regulated during muscle development by the SRF transcription factor. We show that mice lacking either miR-133a-1 or miR-133a-2 are normal, whereas deletion of both miRNAs causes lethal ventricular-septal defects in approximately half of double-mutant embryos or neonates; miR-133a double-mutant mice that survive to adulthood succumb to dilated cardiomyopathy and heart failure. The absence of miR-133a expression results in ectopic expression of smooth muscle genes in the heart and aberrant cardiomyocyte proliferation. These abnormalities can be attributed, at least in part, to elevated expression of SRF and cyclin D2, which are targets for repression by miR-133a. These findings reveal essential and redundant roles for miR-133a-1 and miR-133a-2 in orchestrating cardiac development, gene expression, and function and point to these miRNAs as critical components of an SRF-dependent myogenic transcriptional circuit.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8f4beffedd73fc4f39783be09d7f100dd60f5ad6

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Citations in the corpus

MicroRNA sponges: progress and possibilities. (2010, background): “For miR-133 on the other hand, the knockout mouse does not develop cardiac hypertrophy (Liu et al. 2008) as is observed when a viral sponge construct or antagomirs are delivered to the heart (Carè et al.”
MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. (2009, background): “Similar to the regulation of miR-143/145, SRF directly regulates the expression of the miR-1-1/133a-2 and miR-1-2/133a-1 clusters in developing skeletal and cardiac muscle, and these miRNAs feed back to modulate the actions of SRF in these types of muscle cells through precisely titrated regulatory ”
MicroRNAs in stress signaling and human disease (2012, background): “…multiple aspects of embryonic development (Ventura et al., 2008), miR133a-1 and miR-133a-2, which together are required for appropriate cardiac and skeletal muscle development (Liu et al., 2008, 2011), and miR-208b and miR-499, which coregulate muscle fiber type identity (van Rooij et al., 2009).”
Linking actin dynamics and gene transcription to drive cellular motile functions (2010, neutral): “miR-133, for example, represses the expression of SRF, thereby establishing a negative feedback loop to precisely titrate SRF expression in muscle cell”
Biological functions of microRNAs: a review (2011, background): “Results showed that mice lacking either miR-133a-1 or miR-133a-2 are normal, whereas deletion of both miRNAs causes lethal ventricular-septal defects in approximately one-half of double-mutant embryos or neonates [ 27 ].”
Metazoan MicroRNAs (2018, background): “…(Tatsumi et al., 2016) miR-133 (3) miR-133a-1, miR-133a-2 Perinatal lethality, incomplete penetrance, due to heart defects; adult heart failure (Liu et al., 2008); defective skeletal muscle development and function (Liu et al., 2011); increased browning of white adipose tissue (Liu et al.,…”