SY02-01

The current status of the functional annotations associated with the human genome is in an unfinished state. The majority of current genome annotations are heavily protein coding gene centric. This focus on protein coding genes intrinsically influences current perceptions of how the genome is structured and regulated. This view of the genome also has an underlying supposition that transcripts with very little coding potential are not biologically important. However, recent experiments analyzing the sites of transcription across large sections of the human genome have led to the conclusion that the current human genome annotations can not account for the amounts of empirically detected transcription. (Kapranov, et al. 2002, 2005); Rinn, et al., 2003, Kampa, et al., 2004, Martone, et al., 2003, Cawley et al., 2004Bertone, et al., 2004, Cheng, et. al, 2005 ). Most of the detected unannotated transcription is composed of RNAs with very little coding capacity (<100 aa). Except for the significant reduced coding capacity, these transcripts of unknown function (TUFs) share many properties with well characterized coding genes including: 1) processing of nuclear precursor transcripts (polyadenylation, splicing and nuclear to cytosolic transport), 2) cell type expression specificity, 3) correlation of their 5’ ends with promoter-like sites at which specific regulatory factors and transcription-correlated chromatin modifications are found and 4) temporally regulated expression correlated with cellular differentiation. TUFs have been shown to be nuclear and cytosolic localized as both polyadenylated and non-polyadenylated transcripts (Cheng, et al 2005). The biological functions of these TUFs have begun to be explored using several genetic approaches. Initial results of these functional studies will be described in both human can Drosophila cell systems. These data describe unannotated populations of poly A+ and A-RNA transcripts which comprise a complex architecture for the transcribed regions of the genomes and further indicate significantly more complex strategies for transcriptional regulation than previously anticipated. It may well be that the multifunctional importance of RNA may not have been lost during the evolutionary ascendancy of the functional importance of proteins. This appears to be a lesson to be relearned.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]

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