Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants

T. M. Aune, P. S. Crooke, A. E. Patrick, J. T. Tossberg, N. J. Olsen, C. F. Spurlock

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk. We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets.

Original languageEnglish (US)
Pages (from-to)99-109
Number of pages11
JournalJournal of Autoimmunity
Volume81
DOIs
StatePublished - Jul 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants'. Together they form a unique fingerprint.

Cite this