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Thomas Gingeras

Professor
Ph.D., New York University, 1976

Genome-wide organization of transcription and the functional roles of non-protein coding RNAs

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Gingeras_2011

The RNA repertoire found in each cell is composed of short RNAs and long polyadenylated and non adenylated transcripts. RNA profiles are highly cell type specific and compartmentalized into sub-cellular compartments. Genic and intergenic regions are characterized by overlapping transcription by which the same sequences can be encoded in both protein coding and non-coding transcripts. Characterization of the transcriptomes from many species of organisms has revealed several common features. These include: (1) the copy number of most coding transcripts out number non-coding RNAs but the sequence complexity of non-coding transcripts is greater (2)  non-polyadenylated transcripts are most prevalent in the nucleus and are derived mostly from intergenic regions, (3) the 5' and 3' boundaries of most genes are the origin of promoter associated short RNAs (PASR) and termini associated short RNAS (TASRs), (4) chimeric RNAs are made by cells encoding portions of a genome mapping distally from each chimeric section but joined in a single RNA, (5) the fate of most transcripts is to be processed capped and uncapped short RNAs, (6) recapping of 5' ends of cleavage derived long and short RNAs is common. The functional roles of these various types of RNAs and processes remain unclear. Exploration of these RNAs and process prompt a new view of what a gene is, how genomes are organized and regulated and their possible role in disease.


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Selected Publications

Graveley, B.R., Brooks, A.N., Carlson, J.W., Duff, M.O., Landolin, J., Yanga, L., Artierid, C.,  van Barene, M.J., Booth, B.W., Brown, J. B., Cherbas, L., Davis, C.A.,  Dobin, A., Li, R., Lin, W., Mattiuzzod, N., Miller, D., Sturgill D., Tuch, B.,  Zaleski, C., Zhang, D., Blanchette, M., Cloug, E., Dudoit, S., Eads, B., Green, R.E., Hammonds, A., Kapranov, P., Langtone, L., Malone, J., Perrimon, N., Sandler, J.E., Wan, K.H., Willingham, A., Zhang, Y., Zoug, Y., Andrews, J.,  Brenner, S.E.,  Brent, M., Cherbas, P., Gingeras, T.R., Hoskins, R.A.,  Kaufmani, T., Oliver, B., and Celniker, S.E. 2011. The Developmental Transcriptome of Drosophila melanogaster. Nature 471: 473–479.

The modENCODE Project Consortium. 2010. Identification of functional elements and regulatory circuits in Drosophila by large-scale data integration. Science 330: 1787–1797.

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

The ENCODE Project Consortium 2007. The ENCODE pilot project: identification and analysis of functional elements in 1% of the human genome. 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. Genome-wide RNA Maps Reveal Interlaced Transcript Architecture, New Classes of RNAs and Possible Function for Pervasive Transcription. Science 316: 1484–1488.