From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease

Endocr Rev. 2015 Feb;36(1):25-64. doi: 10.1210/er.2014-1034. Epub 2014 Nov 26.


Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipogenesis / genetics
  • Endocrine Glands
  • Gene Expression
  • Gene Expression Regulation
  • Gene Library
  • Humans
  • Immune System
  • Metabolic Diseases / genetics
  • Muscle, Skeletal
  • Neoplasms / genetics
  • Nervous System
  • RNA, Long Noncoding
  • RNA, Messenger / analysis
  • RNA, Untranslated / genetics
  • RNA, Untranslated / physiology*
  • RNA, Untranslated / therapeutic use
  • Transcriptome


  • HOTAIR long untranslated RNA, human
  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • XIST non-coding RNA