Mir-15 microRNA precursor family

CHEK1

The CHEK1 (checkpoint kinase 1) gene, located at chromosome position 11q24.2, is responsible for encoding the protein kinase Chk1. Chk1 in turn phosphorylates a phosphatase involved in cell cycle control. It mediates the cellular response to DNA replication errors, whilst also playing an important role in the prevention of genetic instability. Elevated CHEK1 levels have been found to be consistent with a lack of miR-15a/16-1 in mice. Postnatal induction of the miR-15 family has been shown to mediate the developmental inactivation of CHEK1 after birth. This inactivation has been identified as a possible contributing factor to the onset of cardiomyocyte binucleation during the neonatal period.

Neonatal cardiomyocyte arrest

Postnatal heart development sees the upregulation of multiple miR-15 family members. In particular, miR-195, when found at higher levels than normal in the developing heart, has been identified as a factor that may cause heart abnormalities in newborns. This has been linked to premature cell cycle arrest, through impaired proliferation of heart muscle fibres and through repressed mitotic gene expression. An accumulation of cardiac muscle fibres sees a consequent block in the transition between the pre-mitotic/G2 phase and mitotic phase of the cell cycle, with postnatal inhibition of the miR-15 family inducing cardiac muscle fibres to enter mitosis. miR-195 overexpression is further associated with cellular hypertrophy.

References

References

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