title: Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions.
abstract: 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.
authors.affiliation: Grup de Recerca en Informática Biomèdica, Institut Municipal d'Investigació Mèdica/Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain.
authors.forename: France
authors.initials: F
authors.lastname: Denoeud
authors.forename: Philipp
authors.initials: P
authors.lastname: Kapranov
authors.forename: Catherine
authors.initials: C
authors.lastname: Ucla
authors.forename: Adam
authors.initials: A
authors.lastname: Frankish
authors.forename: Robert
authors.initials: R
authors.lastname: Castelo
authors.forename: Jorg
authors.initials: J
authors.lastname: Drenkow
authors.forename: Julien
authors.initials: J
authors.lastname: Lagarde
authors.forename: Tyler
authors.initials: T
authors.lastname: Alioto
authors.forename: Caroline
authors.initials: C
authors.lastname: Manzano
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chrast
authors.forename: Sujit
authors.initials: S
authors.lastname: Dike
authors.forename: Carine
authors.initials: C
authors.lastname: Wyss
authors.forename: Charlotte N
authors.initials: CN
authors.lastname: Henrichsen
authors.forename: Nancy
authors.initials: N
authors.lastname: Holroyd
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dickson
authors.forename: Ruth
authors.initials: R
authors.lastname: Taylor
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hance
authors.forename: Sylvain
authors.initials: S
authors.lastname: Foissac
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: Jane
authors.initials: J
authors.lastname: Rogers
authors.forename: Tim
authors.initials: T
authors.lastname: Hubbard
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harrow
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gingeras
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
mesh_terms: D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015894:Genome, Human; D016045:Human Genome Project; D006801:Humans; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D018076:DNA, Complementary