Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire

Mol Cell. 2016 Jun 2;62(5):766-76. doi: 10.1016/j.molcel.2016.03.029.


The life cycle of endogenous retroviruses (ERVs), also called long terminal repeat (LTR) retrotransposons, begins with transcription by RNA polymerase II followed by reverse transcription and re-integration into the host genome. While most ERVs are relics of ancient integration events, "young" proviruses competent for retrotransposition-found in many mammals, but not humans-represent an ongoing threat to host fitness. As a consequence, several restriction pathways have evolved to suppress their activity at both transcriptional and post-transcriptional stages of the viral life cycle. Nevertheless, accumulating evidence has revealed that LTR sequences derived from distantly related ERVs have been exapted as regulatory sequences for many host genes in a wide range of cell types throughout mammalian evolution. Here, we focus on emerging themes from recent studies cataloging the diversity of ERV LTRs acting as important transcriptional regulatory elements in mammals and explore the molecular features that likely account for LTR exaptation in developmental and tissue-specific gene regulation.

Publication types

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

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly
  • DNA Replication
  • DNA, Viral / biosynthesis
  • DNA, Viral / chemistry
  • DNA, Viral / genetics*
  • Endogenous Retroviruses / genetics*
  • Endogenous Retroviruses / growth & development
  • Endogenous Retroviruses / metabolism
  • Gene Expression Regulation, Viral*
  • Host-Pathogen Interactions
  • Humans
  • Promoter Regions, Genetic
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics
  • RNA-Directed DNA Polymerase / metabolism
  • Terminal Repeat Sequences*
  • Transcription, Genetic*
  • Virus Replication*


  • DNA, Viral
  • RNA, Long Noncoding
  • RNA Polymerase II
  • RNA-Directed DNA Polymerase