CONTROL OF RNA

Information about RNA splicing in the biological clock comes mainly from Drosophila. 

In Drosophila, the levels of the genes dper and dtim cycle in a rhythmic manner. The transcription of these genes is indirectly regulated by the corresponding proteins dPER and dTIM (which block the actions of the proteins CYC and dCLK, preventing them from up regulating dper and dtim). 

In addition to the control at the transcriptional level, levels of dper are also controlled at the mRNA level. This is shown by using transgenic flies that are engineered with a null (inactive) gene and various lengths of promoter-less genomic fragments from the per gene. A length of per gene 7.2 kb restores rhythms in the Drosophila dper mutant (Frisch et al 1994). As the gene is a null copy, there is no negative feedback, so transcription itself is not rhythmic. The cycling in the mRNA must therefore occur at the mRNA stage. It is thought that there is a difference between the half life of the dper mRNA during the phase when it is accumulating and when it is declining (Harmer et al. 2000). 

Control of the cycling of dper at the mRNA level has been shown in the adaptation of Drosophila to cold. There are 2 possible dper mRNA transcripts possible, these are created by alternative splicing of the dper mRNA in a 3’ area that is not translated into protein. At low temperatures, removal of this 3’ untranslated region (UTR) is stimulated. This causes an advance in the phases of both the mRNA and protein cycles. The accumulation of dPER is partially dependent on the presence of dTIM. As dTIM is photosensitive, the effect of cold on dper can largely be counteracted by the effect on long days on dTIM (Majercak et al. 1999).

                       

Accessibility statement