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” provi...

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Bibliographic Details
Published in:Molecular cell 2016-06, Vol.62 (5), p.766-776
Main Authors: Thompson, Peter J., Macfarlan, Todd S., Lorincz, Matthew C.
Format: Article
Language:English
Subjects:
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
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Summary: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. Solitary long terminal repeats (LTRs) have been frequently domesticated into gene regulatory elements in mammals. Here, Thompson et al. evaluate the features of LTRs that account for the prevalence of this phenomenon and highlight recent studies providing insight into the molecular mechanisms that influence the exaptation of LTRs.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2016.03.029