Mir-8/mir-141/mir-200 Micro RNA Precursor Family - Targets of MiR-8

Targets of MiR-8

The atrophin gene has been shown to be a target of Drosophila miR-8., with suggestion that this target is also conserved in mammalian miR-8. Elevated atrophin activity in miR-8 mutant phenotypes has been observed, this in turn inducing elevated neural apoptosis and also behavioural defects. The atrophin mRNA increase in miR-8 mutants occurs post-transcriptionally, with miR-8 binding leading to destabilisation of atrophin mRNA. miR-8 acts to control atrophin expression in vivo directly via miR-8 sites in its 3'UTR. Indeed, a statistically significant increase in surviving adults following the removal of one copy of the atrophin gene has shown atrophin mRNA to be a functionally important target in vivo. This supports the theory that a misregulation of atrophin contributes to the defects seen in miR-8 mutants. Atrophin protein levels have additionally been found to be detectably higher in miR-8 mutant brains. The neural effects of miR-8 in miR-8-expressing cells are likely to be concentrated in miR-8-expressing neurons, therefore only acting to affect certain neuron functions.

A tuning target relationship is in place between atrophin levels and miR-8 regulation. The level of atrophin below that reached by miR-8 regulation is detrimental for the continued functioning of miR-8-expressing cells. The atrophin level here is required at an optimal level to ensure the avoidance of developmental defects arising due to decreased atrophin expression.

The human miR-200c is likely to target the Zinc Finger Transcription Factor 8 (TCF8) gene.