Thomas R. Gingeras, Ph.D., Cold Spring Harbor Laboratory

Please visit the Gingeras Lab home page

Click to Enlarge Graphic
Three levels of resolution illustrating composition of pervasive transcription. The clustering of genes in the top-most panel presents the non-uniform distribution of protein coding genes in the genome and illustrate the canonical view of gene organization. Arrows illustrate direction of transcription of genes on both strands. The middle panel illustrates the interleaved nature of coding and non-coding transcription observed across and between genic regions. These transcripts also highlight the multiple regulatory regions (triangles) that exist within and between genes regulating the expression of these overlapping RNAs. The ultimate fate of some of these long transcripts (e.g. promoter associated long RNAs –PALRs) is to provide short RNAs such as micro (mi) RNAs, promoter associated short RNAs (PASRs), termini associated short RNAs (TASRs) as depicted in the lower panel.

Thomas R. Gingeras
Professor
Head of Functional Genomics
Ph.D., New York University, 1976
Genome-wide organization of transcription and the functional roles of non-protein coding RNAs

email gingeras@cshl.edu, (516) 422-4105, fax (516) 422-4109

Genomes from yeast to man are almost completely tr anscribed. The RNA repertoire found in each cell is highly individualized and consists of overlapping RNAs in which the same sequences are encoded in protein coding and non-coding transcripts. We have developed genome-wide transcription maps in many cell types. Our biochemical characterization of the mapped transcripts has revealed several common features. These include: 1) the number of RNA isoforms for protein coding genes is significantly underestimated relative to what most databases indicate, 2) more than 70% of all protein coding genes have at least one antisense transcript overlapping the coding transcript, 3) the 5’ and 3’ boundaries of most protein coding genes can be positioned hundreds of thousands to millions of base pairs away from the annotated ends of a gene, 4) chimeric RNAs are made by eukaryotic cells encoding portions of a genome mapping at great distances from each chimeric section but joined in a single RNA, 5) the fate of many coding and nc-transcripts is to be cleaved, the 5’ ends of their cleavage products capped and the capped cleaved long RNAs clipped to form capped short RNAs and 6) the 5’ and 3’ ends of protein coding genes are sites at which collections of regulatory promoter associated short RNAs (PASRs) can be found. Many questions have emerged concerning this pervasive transcription. Answers to these questions will provide a new view of what a gene is, how genomes are organized and regulated and their possible role in disease.

Please visit Tom's Lab home page.

Selected Publications

Fejes-Toth, K*., Kapranov, P*., Foissac, S., K, Sotirova, V., Sachidanandam, R., Willingham, A.T., Duttagupta, R., Dumais, E., Hannon, G.J. and Gingeras, T.R. 2009 Post-transcriptional processing generates a diversity of 5’-modified long and short RNAs. Nature 457:1028-1032.

Efroni, S., Duttagupta, R.., Cheng, J., Dehghan, H., Hopepner D.J., Dash C., Bazett-Jones D.P., Le Grice S., McKay, R.D.G., Buetow. K., Gingeras, T.R., Misteli, T. and Meshorer, E. .2008. Global transcriptional activity in pluripotent embryonic stem cell. Cell Stem Cell 2: 437-447.

The ENCODE Project Consortium 2007 Identification and analysis of functional elements in 1% of the human genome by the ENCODE project. Nature 447: 799-816.

Kapranov, P., Cheng, J., Dike, S.,Nix, D., Duttagupta, R., Willingham, A. T., Stadler, P., Hertel, J., Hackermueller, J., Hofacker, I. L., Bell, I., Cheung, E., Drenkow, J., Dumais, E., Patel, S., Helt, G., Madhavan, G., Ghosh, S., Piccolboni, A., Sementchenko, V., Tammana, H., and Gingeras, T. R. 2007. RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription. Science 316: 1484-1488.

Cheng, J., Kapranov, P., Drenkow, J., Dike, S., Brubaker, S., Patel, S., Long, J., Stern, D., Tammana, H., Helt, G., Sementchenko, V.S., Piccolboni, A., Bekiranov, S., Bailey, D. K., Ganesh, M., Ghosh, S., Gerhard, D.S. and Gingeras, T. R 2005. Transcriptional maps of 10 human chromosomes at 5 nucleotide resolution. Science 308: 1149-1154.