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

Tanay Ghosh; Rafael Gois De 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 R 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

Tanay Ghosh^*, Rafael Gois De 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 R Adams, Bernard Zalc, Nick Goldman, David A Lyons^*, Robin J M Franklin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	814-830.e23
Journal	Cell
Volume	187
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2024.01.011
Publication status	Published - 15 Feb 2024

Keywords / Materials (for Non-textual outputs)

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

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10.1016/j.cell.2024.01.011

Ghosh_et_al_manuscriptAccepted author manuscript, 7.09 MB

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Ghosh, T., Gois De Almeida, R., Zhao, C., Mannioui, A., Martin, E., Fleet, A., Chen, C. Z., Assinck, P., Ellams, S., Gonzalez, G. A., Graham, S. C., Rowitch, D. H., Stott, K., Adams, I. R., Zalc, B., Goldman, N., Lyons, D. A., & Franklin, R. J. M. (2024). A retroviral link to vertebrate myelination through retrotransposon RNA-mediated control of myelin gene expression. Cell, 187(4), 814-830.e23. https://doi.org/10.1016/j.cell.2024.01.011

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

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 = "myelination, transposable element, retrotransposon, long terminal repeat, LTR, endogenous retrovirus, ERV, convergent evolution, oligodendrocyte, oligodendrocyte progenitor cells",

author = "Tanay Ghosh and {Gois De Almeida}, Rafael and Chao Zhao and Abdelkrim Mannioui and Elodie Martin and Alex Fleet and Chen, {Civia Z.} and Peggy Assinck and Sophie Ellams and Gonzalez, {Ginez A.} and Graham, {Stephen C} and Rowitch, {David H} and Katherine Stott and Adams, {Ian R} and Bernard Zalc and Nick Goldman and Lyons, {David A} and Franklin, {Robin J M}",

year = "2024",

month = feb,

day = "15",

doi = "10.1016/j.cell.2024.01.011",

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journal = "Cell",

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Ghosh, T, Gois De Almeida, R, Zhao, C, Mannioui, A, Martin, E, Fleet, A, Chen, CZ, Assinck, P, Ellams, S, Gonzalez, GA, Graham, SC, Rowitch, DH, Stott, K, Adams, IR, Zalc, B, Goldman, N, Lyons, DA & Franklin, RJM 2024, 'A retroviral link to vertebrate myelination through retrotransposon RNA-mediated control of myelin gene expression', Cell, vol. 187, no. 4, pp. 814-830.e23. https://doi.org/10.1016/j.cell.2024.01.011

TY - JOUR

T1 - A retroviral link to vertebrate myelination through retrotransposon RNA-mediated control of myelin gene expression

AU - Ghosh, Tanay

AU - Gois De Almeida, Rafael

AU - Zhao, Chao

AU - Mannioui, Abdelkrim

AU - Martin, Elodie

AU - Fleet, Alex

AU - Chen, Civia Z.

AU - Assinck, Peggy

AU - Ellams, Sophie

AU - Gonzalez, Ginez A.

AU - Graham, Stephen C

AU - Rowitch, David H

AU - Stott, Katherine

AU - Adams, Ian R

AU - Zalc, Bernard

AU - Goldman, Nick

AU - Lyons, David A

AU - Franklin, Robin J M

PY - 2024/2/15

Y1 - 2024/2/15

N2 - 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.

AB - 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.

KW - myelination

KW - transposable element

KW - retrotransposon

KW - long terminal repeat

KW - LTR

KW - endogenous retrovirus

KW - ERV

KW - convergent evolution

KW - oligodendrocyte

KW - oligodendrocyte progenitor cells

U2 - 10.1016/j.cell.2024.01.011

DO - 10.1016/j.cell.2024.01.011

M3 - Article

SN - 0092-8674

VL - 187

SP - 814-830.e23

JO - Cell

JF - Cell

IS - 4

ER -

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

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Keywords / Materials (for Non-textual outputs)

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