Human 3'UTRome Encyclopedia
We have learned a lot from worms about 3'UTR RNA biology. Having the full 3'UTRome allows us to study PAS elements, miRNA targets, and alternative polyadenylation with a precision unthinkable a few years ago. In addition to the sequences, we developed a genomic 3'RACE pipeline and cloned at least one 3'UTR isoform for every protein-coding gene. This library is the first for a metazoan organism, and it allows for the first time the investigation of post-transcriptional gene regulation in vivo using high-throughput downstream analyses.
In human, unfortunately, we still do not have a complete cloned 3'UTRome. The extent of alternative polyadenylation is still largely unknown but estimated to occur in at least half of the transcriptomes. The majority of the data available comes from the re-annotation of ESTs and other genomic approaches, but nobody has tackled this question systematically, yet, using a multi-pronged approach as we did in worms.
We are exploring the possibility to prepare a human 3'UTRome library, and clone at least one 3'UTR for each of the ~20K human protein coding genes (See figure 4). A complete human 3'UTRome library would be an incredible milestone in genome biology, an invaluable tool to study transcriptional termination, probe miRNA biology, study RNA binding protein elements and post-transcriptional gene regulation, and to better understand the biology of these gene portions in human disease. The price tag of such a venture would actually be quite small, especially considering that the cost of high-throughput technologies halves every 5 years.
The human 3'UTRome resource will be publically available to the community, and will provide the foundation for further analysis of 3'UTR involvement in the broad range of human disease that they have been implicated in, including diabetes, Alzheimer's and cancer.