Defining RNA polymerase II transcription units across the mammalian genome
Year of award: 2019
Grantholders
Prof Nicholas Proudfoot
University of Oxford
Project summary
The ease of sequencing human genomes has greatly outstripped understanding of how genes actually work. While between 20,000–30,000 genes generate transcripts that directly encode proteins, many more produce non-coding transcripts, often degraded as they are made.
We will redress the knowledge imbalance between genome sequence and gene mechanism by focusing on transcriptional termination, a process that separates one gene from the next along a chromosome. In particular we will investigate how genes normally terminate as many cases of cellular pathology, such as viral infection and cancer, are associated with a breakdown in this process. We will also study a novel mechanism that initiates transcription of non-coding genes and is likely to explain why these transcripts are so numerous.
We predict that while many non-coding genes have no particular function for the cell, they are likely to be important as an evolutionary resource that allows for the creation of new functional genes.