A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression

Tanay Ghosh; Rafael G Almeida; Chao Zhao; Abdelkrim Mannioui; Elodie Martin; Alex Fleet; Civia Z Chen; Peggy Assinck; Sophie Ellams; Ginez A Gonzalez; Stephen C Graham; David H Rowitch; Katherine Stott; Ian Adams; Bernard Zalc; Nick Goldman; David A Lyons; Robin J M Franklin

doi:10.1016/j.cell.2024.01.011

A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression

Cell. 2024 Feb 15;187(4):814-830.e23. doi: 10.1016/j.cell.2024.01.011.

Authors

Tanay Ghosh¹, Rafael G Almeida², Chao Zhao³, Abdelkrim Mannioui⁴, Elodie Martin⁵, Alex Fleet⁶, Civia Z Chen³, Peggy Assinck³, Sophie Ellams⁷, Ginez A Gonzalez⁶, Stephen C Graham⁸, David H Rowitch⁹, Katherine Stott¹⁰, Ian Adams¹¹, Bernard Zalc⁵, Nick Goldman¹², David A Lyons², Robin J M Franklin¹³

Affiliations

¹ Altos Labs-Cambridge Institute of Science, Cambridge CB21 6GP, UK; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: writetotanay@gmail.com.
² Centre for Discovery Brain Sciences, MS society Edinburgh Centre for MS Research, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
³ Altos Labs-Cambridge Institute of Science, Cambridge CB21 6GP, UK; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AW, UK.
⁴ Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), Aquatic Facility, 75005 Paris, France.
⁵ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.
⁶ Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AW, UK.
⁷ Altos Labs-Cambridge Institute of Science, Cambridge CB21 6GP, UK.
⁸ Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
⁹ Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.
¹⁰ Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.
¹¹ MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
¹² European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome, Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
¹³ Altos Labs-Cambridge Institute of Science, Cambridge CB21 6GP, UK; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: rfranklin@altoslabs.com.

PMID: 38364788
DOI: 10.1016/j.cell.2024.01.011

Abstract

Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.

Keywords: ERV; LTR; convergent evolution; endogenous retrovirus; long terminal repeat; myelination; oligodendrocyte; oligodendrocyte progenitor cells; retrotransposon; transposable element.

MeSH terms

Animals
Anura
Gene Expression
Myelin Sheath* / metabolism
Oligodendroglia / metabolism
RNA / metabolism
Retroelements* / genetics
Zebrafish / genetics

Substances

Retroelements
RNA

Abstract

MeSH terms

Substances

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