Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire.
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.
Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Peter J
PJ
Thompson
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Electronic address: todd.macfarlan@nih.gov.
Todd S
TS
Macfarlan
Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: mlorincz@mail.ubc.ca.
Matthew C
MC
Lorincz
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic; D014779:Virus Replication
D004279:DNA, Viral; D062085:RNA, Long Noncoding; D012319:RNA Polymerase II; D012194:RNA-Directed DNA Polymerase