Pathways to tumour formation
Recent evidence indicates that tumours express a family of proteins that contain four related transcription factors known as inhibitors of differentiation (Id). Id proteins bind and regulate various other transcription factors thereby affecting cell proliferation and oncogenic transformation. RNA polymerase (pol) III transcribes short non-coding genes essential for protein synthesis such as RNAs that transfer amino acids (tRNAs). It is also believed to play a role in cancer formation. Scientists on the EU-funded ID AND POL III (Regulation of RNA polymerase III transcription by Id proteins and E47) project worked to identify a link between Id proteins and RNA pol III transcription. Their work showed that one of the Id proteins binds together with the cell cycle inhibitor E47 onto RNA pol III transcribed genes. E47 binds to a consensus DNA sequence that is located near tRNA genes in the human genome. Using specialised assays, researchers also proved that E47 binds to members of the RNA pol III transcription complex, including Id2, and brings them onto RNA pol III-transcribed genes. However, the impact of E47 on transcription is repressive indicating an antagonism with Id proteins, which act as positive regulators of RNA pol III transcription. Based on their results, scientists proposed a mechanism of RNA pol III transcription. Under conditions of reduced cellular output, E47 is recruited by the RNA pol III transcription complex onto transcribed genes. These genes are converted to a repressed state through alteration of the chromatin environment. When conditions become favourable again, E47 recruits Id2 to upregulate RNA pol III transcription. Collectively, the findings of the ID AND POL III study shed light on RNA pol III transcription and identified a novel way to control it. Given the potential role of Id proteins in cancer, the project may open up avenues for further elucidating the mechanisms of carcinogenesis.
