Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions.

TitleProminent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions.
Publication TypeJournal Article
Year of Publication2007
AuthorsDenoeud, F, Kapranov, P, Ucla, C, Frankish, A, Castelo, R, Drenkow, J, Lagarde, J, Alioto, T, Manzano, C, Chrast, J, Dike, S, Wyss, C, Henrichsen, CN, Holroyd, N, Dickson, MC, Taylor, R, Hance, Z, Foissac, S, Myers, RM, Rogers, J, Hubbard, T, Harrow, J, Guigó, R, Gingeras, TR, Antonarakis, SE, Reymond, A
JournalGenome Res
Date Published2007 Jun
KeywordsChromosome Mapping, DNA, Complementary, Exons, Genome, Human, Human Genome Project, Humans, Open Reading Frames, Promoter Regions, Genetic, Quantitative Trait Loci, Transcription, Genetic

This report presents systematic empirical annotation of transcript products from 399 annotated protein-coding loci across the 1% of the human genome targeted by the Encyclopedia of DNA elements (ENCODE) pilot project using a combination of 5' rapid amplification of cDNA ends (RACE) and high-density resolution tiling arrays. We identified previously unannotated and often tissue- or cell-line-specific transcribed fragments (RACEfrags), both 5' distal to the annotated 5' terminus and internal to the annotated gene bounds for the vast majority (81.5%) of the tested genes. Half of the distal RACEfrags span large segments of genomic sequences away from the main portion of the coding transcript and often overlap with the upstream-annotated gene(s). Notably, at least 20% of the resultant novel transcripts have changes in their open reading frames (ORFs), most of them fusing ORFs of adjacent transcripts. A significant fraction of distal RACEfrags show expression levels comparable to those of known exons of the same locus, suggesting that they are not part of very minority splice forms. These results have significant implications concerning (1) our current understanding of the architecture of protein-coding genes; (2) our views on locations of regulatory regions in the genome; and (3) the interpretation of sequence polymorphisms mapping to regions hitherto considered to be "noncoding," ultimately relating to the identification of disease-related sequence alterations.

Alternate JournalGenome Res.
PubMed ID17567994
PubMed Central IDPMC1891335
Grant ListU01 HG003147 / HG / NHGRI NIH HHS / United States
U01HG03147 / HG / NHGRI NIH HHS / United States
N01C012400 / / PHS HHS / United States
U01HG03150 / HG / NHGRI NIH HHS / United States
077198 / / Wellcome Trust / United Kingdom
N01CO12400 / CA / NCI NIH HHS / United States
U01 HG003150 / HG / NHGRI NIH HHS / United States