Structural potential of the 5′ noncoding regions of the mRNAs encoding p53 isoforms

Famous for its nickname "guardian of the genome," the p53 protein acts, among other things, as a transcription factor in the form of a tetramer, which may consist of different types of p53 isoforms. They differ in length and content of specific domains that are responsible for their functions. The way this factor acts, sometimes opposite to what we would expect from the main protein isoform, depends on which isoforms form the tetramer. There are over a dozen isoforms of the human p53 protein encoded by a single gene, thanks to the use of different transcriptional promoters (DNA level), alternative splicing (pre-mRNA level), and different translation initiation sites (mRNA level). <i>In vitro</i> studies have demonstrated that the use of different translation initiation sites on full-length p53FL mRNA is possible due to specific RNA structures, and that these structures are also responsible for the rate and efficiency of target protein isoform formation. This affects the proportions between the different p53 isoforms present in the cell at a given moment and, consequently, the further fate of the cell. This paper summarizes the knowledge about the importance of the RNA structure (I-III order) of individual p53 transcripts for the fate of the cell and the organism.