Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin.
BACKGROUND
Although analysis pipelines have been developed to use RNA-seq to identify long non-coding RNAs (lncRNAs), inference of their biological and pathological relevance remains a challenge. As a result, most transcriptome studies of autoimmune disease have only assessed protein-coding transcripts.


RESULTS
We used RNA-seq data from 99 lesional psoriatic, 27 uninvolved psoriatic, and 90 normal skin biopsies, and applied computational approaches to identify and characterize expressed lncRNAs. We detect 2,942 previously annotated and 1,080 novel lncRNAs which are expected to be skin specific. Notably, over 40% of the novel lncRNAs are differentially expressed and the proportions of differentially expressed transcripts among protein-coding mRNAs and previously-annotated lncRNAs are lower in psoriasis lesions versus uninvolved or normal skin. We find that many lncRNAs, in particular those that are differentially expressed, are co-expressed with genes involved in immune related functions, and that novel lncRNAs are enriched for localization in the epidermal differentiation complex. We also identify distinct tissue-specific expression patterns and epigenetic profiles for novel lncRNAs, some of which are shown to be regulated by cytokine treatment in cultured human keratinocytes.


CONCLUSIONS
Together, our results implicate many lncRNAs in the immunopathogenesis of psoriasis, and our results provide a resource for lncRNA studies in other autoimmune diseases.
Lam C
LC
Tsoi
Matthew K
MK
Iyer
Philip E
PE
Stuart
William R
WR
Swindell
Johann E
JE
Gudjonsson
Trilokraj
T
Tejasvi
Mrinal K
MK
Sarkar
Bingshan
B
Li
Jun
J
Ding
John J
JJ
Voorhees
Hyun M
HM
Kang
Rajan P
RP
Nair
Arul M
AM
Chinnaiyan
Goncalo R
GR
Abecasis
James T
JT
Elder
D016000:Cluster Analysis; D019295:Computational Biology; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D012867:Skin / Q000378:metabolism*; D059467:Transcriptome
D062085:RNA, Long Noncoding