Alternative titles; symbolsmiRNA199A1MIRN199A1HGNC Approved Gene Symbol: MIR199A1Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38): 19:10,817,425-10...
Alternative titles; symbols
HGNC Approved Gene Symbol: MIR199A1
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38): 19:10,817,425-10,817,495 (from NCBI)
MicroRNAs (miRNAs), such as miR199A, are noncoding RNAs of 20 to 25 nucleotides that regulate gene expression. Two distinct genes, MIRN199A1 and MIRN199A2 (610720), encode the same mature miR199A sequence (Fu et al., 2005).
▼ Cloning and Expression
Fu et al. (2005) cloned miR199A from a human fetal liver cDNA library. The miR199A sequence is CCCAGUGUUCAGACUACCUGUUC.
▼ Gene Function
Using microarray analysis, van Rooij et al. (2006) identified miR199A among a group of miRNAs upregulated in 2 independent mouse models of cardiac hypertrophy. Northern blot analysis showed increased expression of miR199A in idiopathic end-stage failing human hearts. Overexpression of miR199A in cultured rat cardiomyocytes resulted in a pronounced morphologic response in which cardiomyocytes became elongated.
Eulalio et al. (2012) showed that the exogenous administration of selected miRNAs markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. Eulalio et al. (2012) performed a high-content microscopy, high-throughput function screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs, miR590 (615070) and miR199a, were further selected for testing and were shown to promote cell cycle reentry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters.
Gabisonia et al. (2019) showed that expression of human miR199A in infarcted pig hearts can stimulate cardiac repair. One month after myocardial infarction and delivery of this microRNA through an adeno-associated viral vector, treated animals showed marked improvements in both global and regional contractility, increased muscle mass, and reduced scar size. These functional and morphologic findings correlated with cardiomyocyte dedifferentiation and proliferation. However, subsequent persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs. Such events were concurrent with myocardial infiltration of proliferating cells displaying a poorly differentiated myoblastic phenotype. Gabisonia et al. (2019) concluded that although cardiac repair through the stimulation of endogenous cardiomyocyte proliferation is attainable in large mammals, dosage of this therapy needs to be tightly controlled.
Fu et al. (2005) stated that miR199A is encoded by genes on chromosome 19 (MIRN199A1) and chromosome 1 (MIRN199A2).