TRANSLATIONAL CONTROL

As well as control at the transcript level (i.e. mRNA), every biological clock shows some level of translational control (i.e. control at the protein level).

In every known clock system, there is at least 1 instance where there is a delay between the peak levels of mRNA and the peak levels of the resulting protein. In cyanobacteria it is KaiB and KaiC, in Neurospora it is FRQ, in Drosophila it is dPER and dTIM and in mammals it is mPER1 and mPER2 (Harmer et at 2001). It is thought that this delay may be to allow enough mRNA to be synthesised to keep the clock “ticking” before the gene is repressed. The exact mechanisms that cause the delays for the most part are unclear.

In Drosophila, it is thought that the delay seen with dper is partly due to the instability of dPER in the absence of dTIM. This instability is caused by the protein Dbt from the gene double-time dbt). If this is the case, the delay is less due to dPER than it is to do with dTIM, as it is the presence of dTIM is the rate limiting step (Price et al 1998).

Other examples of post translation control can be seen with the protein WC-1 in Neurospora and in mCRY2 in mice. Although the transcription of wc-1 and mcry2 is not rhythmic, the protein levels are. This suggests some form of post-translational control, although the mechanism is not clear. This is because there are many different possibilities as to how this is achieved, such as 5’ UTR-mediated control, mechanisms in the 3’ UTRs or the Poly (A) tail, or modulation of the initiation machinery by phosphorylation (Gray and Wickens, 1998).  

                       

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