Mouse

Measuring and interpreting transposable element expression

AbstractTransposable elements (TEs) are insertional mutagens that contribute greatly to the plasticity of eukaryotic genomes, influencing the evolution and adaptation of species as well as physiology or disease in individuals. Measuring TE expression helps to understand not only when and where TE mobilization can occur but also how this process alters gene expression, chromatin accessibility or cellular signalling pathways. Although genome-wide gene expression assays such as RNA sequencing include transposon-derived transcripts, most computational analytical tools discard or misinterpret TE-derived reads. Emerging approaches are improving the identification of expressed TE loci and helping to discriminate TE transcripts that permit TE mobilization from chimeric gene–TE transcripts or pervasive transcription. Here we review the main challenges associated with the detection of TE expression, including mappability, insertional and internal sequence polymorphisms, and the diversity of the TE transcriptional landscape, as well as the different experimental and computational strategies to solve them.

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Download referencesAcknowledgementsThe authors apologize to the many colleagues who have made significant contributions to the field but whose work could not be cited or discussed owing to space limitations. The authors are grateful to P. A. Defossez and A. Doucet for critical reading of the manuscript. This work was supported by grants to G.C. from the Fondation pour la Recherche Médicale (DEQ20180339170), the Agence Nationale de la Recherche (LABEX SIGNALIFE, ANR-11-LABX-0028-01; RetroMet, ANR-16-CE12-0020; ImpacTE, ANR-19-CE12-0032), the Canceropôle Provence–Alpes–Côte d’Azur, the French National Cancer Institute (INCa) and the Provence–Alpes–Côte d’Azur Region, CNRS (GDR 3546), and the University Hospital Federation (FHU) OncoAge.Author informationAffiliationsUniversité Côte d’Azur, Inserm, CNRS, IRCAN, Nice, FranceSophie Lanciano & Gael CristofariContributionsThe authors contributed equally to all aspects of the article.Corresponding authorCorrespondence to
Gael Cristofari.Ethics declarations

Competing interests
G.C. is an unpaid associate editor of the journal Mobile DNA (Springer Nature). S.L. declares no competing interests.

Additional informationPeer review informationNature Reviews Genetics thanks G. J. Faulkner and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.Publisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.GlossaryAutonomous TE unit transcription
TE transcription driven by its own internal promoter.
Chimeric transcripts
Transcripts containing both TE and non-TE (typically a gene) sequences.
Co-transcription
Intronic TE expression through the expression of its surrounding gene without the implication of the promoter activity of the TE. Synonymous with ‘readthrough transcription’.
Polymorphic
A term often used for TE insertional polymorphisms, whereby a TE insertion can be present or absent at a given locus or allele in a subset of individuals from the same species.
Positive selection
A type of natural selection that promotes the spread of a beneficial trait or genetic variant within a given population.
Long terminal repeat (LTR) retrotransposons
A class of retrotransposons that contains two long repeated sequences in direct orientation at both ends.
TE unit-length transcripts
Full-length TE transcripts that can serve as a template for reverse transcription to produce a new intact copy.
Pervasive transcription
Transcription of regions well beyond the boundaries of known genes.
Multimappers
Sequencing reads that map ambiguously at multiple locations in the reference genome.
Unimappers
Sequencing reads that can map non-ambiguously to a single location in the reference genome.
k-mers
Short sequences with a length of k bases.
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