The human genome contains many thousands of long noncoding RNAs (lncRNAs). While 
several studies have demonstrated compelling biological and disease roles for 
individual examples, analytical and experimental approaches to investigate these 
genes have been hampered by the lack of comprehensive lncRNA annotation. Here, 
we present and analyze the most complete human lncRNA annotation to date, 
produced by the GENCODE consortium within the framework of the ENCODE project 
and comprising 9277 manually annotated genes producing 14,880 transcripts. Our 
analyses indicate that lncRNAs are generated through pathways similar to that of 
protein-coding genes, with similar histone-modification profiles, splicing 
signals, and exon/intron lengths. In contrast to protein-coding genes, however, 
lncRNAs display a striking bias toward two-exon transcripts, they are 
predominantly localized in the chromatin and nucleus, and a fraction appear to 
be preferentially processed into small RNAs. They are under stronger selective 
pressure than neutrally evolving sequences-particularly in their promoter 
regions, which display levels of selection comparable to protein-coding genes. 
Importantly, about one-third seem to have arisen within the primate lineage. 
Comprehensive analysis of their expression in multiple human organs and brain 
regions shows that lncRNAs are generally lower expressed than protein-coding 
genes, and display more tissue-specific expression patterns, with a large 
fraction of tissue-specific lncRNAs expressed in the brain. Expression 
correlation analysis indicates that lncRNAs show particularly striking positive 
correlation with the expression of antisense coding genes. This GENCODE 
annotation represents a valuable resource for future studies of lncRNAs.