RT Journal
A1 Denoeud, France
A1 Kapranov, Philipp
A1 Ucla, Catherine
A1 Frankish, Adam
A1 Castelo, Robert
A1 Drenkow, Jorg
A1 Lagarde, Julien
A1 Alioto, Tyler
A1 Manzano, Caroline
A1 Chrast, Jacqueline
A1 Dike, Sujit
A1 Wyss, Carine
A1 Henrichsen, Charlotte N.
A1 Holroyd, Nancy
A1 Dickson, Mark C.
A1 Taylor, Ruth
A1 Hance, Zahra
A1 Foissac, Sylvain
A1 Myers, Richard M.
A1 Rogers, Jane
A1 Hubbard, Tim
A1 Harrow, Jennifer
A1 Guigó, Roderic
A1 Gingeras, Thomas R.
A1 Antonarakis, Stylianos E.
A1 Reymond, Alexandre
T1 Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions
JF Genome Research 
JO Genome Research 
YR 2007 
FD June 01 
VO 17 
IS 6 
SP 746 
OP 759 
DO 10.1101/gr.5660607 
UL http://genome.cshlp.org/content/17/6/746.abstract 
AB 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.