The importance of protein concentration control
Proteins are built on transfer RNA (tRNA) molecules. The basic mechanism is that transcription factor (TF) IIIC (TFIIIC), otherwise known as tau, binds to a special regulatory zone on the tRNA genes. Another transcription factor TFIIIB together with Pol III can then initiate transcription. The EXTRATF (Global positioning of TFIIIC and its involvement in extra-transcriptional processes (ExtraTF)) project has looked into the molecular mechanics of TFIIIC. Using in vivo fluorescence cross-correlation spectroscopy and fluorescently tagged proteins, they have investigated how TFIIIC regulates the different tRNAs. TFIIIC has many subunits and is therefore multifunctional. The subunits exist in the nucleus and the cytoplasm in similar numbers. However, they have affinity to each other and exist as active complexes mainly in the nucleus. Researchers found that there is a special relationship between two of the subunits, tau138 and tau55, whereby tau55 needs the presence of tau138. Absence means that tau55 relocates into the cytoplasm. Using six specially designed degron strains that dictate the starting place of degradation in a sequence of amino acids, EXTRATF looked into the function of TFIIIC. By degrading each subunit of the TFIIIC complex in turn, they showed that this increased the transcription of tRNAs. However, transcription of other Pol III-transcribed RNAs shows no change. Interestingly, this indicates that there is another type of transcription regulation that needs TFIIIC apart from Pol III. Final experiments to confirm this exciting find are still ongoing and are in collaboration with the partner company EMBL, Heidelberg. The impact of this work is highly significant for diseases that involve mistakes in transcription levels such as cancer and neurodegeneration. Different expression levels of tRNA can be used as biomarkers for diagnosis.
Keywords
Protein, cancer, tRNA, TFIIIC, tau
