When a gene is activated, it is copied (transcribed) from DNA into a string of molecules called a messenger RNA (mRNA). The middle section of each mRNA encodes the information that is translated into the corresponding protein sequence; the two ends, called untranslated regions (UTRs), play a number of other important roles. This proposal concerns the tail end of the mRNA, known as the 3' UTR, which helps to regulate the stability and location of the mRNA and the amount of the corresponding protein that is produced. The point at which the transcription of a given mRNA ends is determined by the presence of a sequence called a polyadenylation site. Some genes have more than one such site, meaning that there can be two or more different forms of the corresponding mRNA, with different 3' UTRs and therefore different levels of activity. Changes in the ratio of the different forms are thought to contribute to the development of a range of disorders, including some cancers. The methods currently used to study polyadenylation require an extra set of experiments to be run, which is expensive and slow. However, Drs. Birol and Karsan and their teams have obtained evidence that polyadenylation can be studied alongside other important types of transcriptional regulation, using data from experiments that are already performed as part of standard analysis. This will make studies of polyadenylation sites affordable by more laboratories, and will add value to existing data.
When a gene is activated, it is copied ('transcribed') from DNA into a string of molecules called a messenger RNA (mRNA), which has three sections: the middle section encodes the information that is translated into the corresponding protein sequence, and the two ends, called untranslated regions (UTRs), play a number of other important roles. Drs. Birol and Karsan propose to develop a new method to analyze the tail ends of mRNAs, known as the 3' UTRs, which help to regulate the stability and location of the mRNA and the amount of the corresponding protein that is produced. Changes to the 3' UTRs of some genes are thought to contribute to the development of cancers and other diseases, and the new method will be used to study the features of these regions to understand their role in this process.
| Xue, Zhuyi; Warren, René L; Gibb, Ewan A et al. (2018) Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes. BMC Genomics 19:536 |
| Birol, Inanç; Raymond, Anthony; Chiu, Readman et al. (2015) Kleat: cleavage site analysis of transcriptomes. Pac Symp Biocomput :347-58 |
