Tanay Ghosh (Altos Labs Cambridge), Thursday 18th April 1pm-2pm, Rayne Second Floor Seminar Room

Tanay Ghosh (Altos Labs Cambridge)
“RetroMyelin: a retroviral role in the evolution of the vertebrate myelination program"

Thursday 18th April 1-2pm
Rayne Building (2^nd floor seminar room) 5 University Street.

Myelin is the spiral membrane wrapping around axons in the central and peripheral nervous systems of vertebrates.  Myelin provides electrical insulation and greatly increases (100x) the speed of propagation of action potentials (electrical impulses), at the same time conserving energy.  In so doing myelin greatly increases the speed of communication across the body and brain, allowing for faster responses, enhanced computational power and increased size of both body and brain.  There is a temporal correlation between the evolutionary emergence of myelin and the vertebrate jaw; jawless vertebrates conspicuously lack myelin, leading to the idea that the primary selection for myelin was evolution of predatory behaviour in vertebrates and/or the ability to escape from predation.  Hence, the appearance of myelin in gnathosomes marked a pivotal moment in vertebrate evolution.

My research establishes a crucial connection between myelination and the RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, emphasizing its central role in this biological process. I have unravelled a mechanism in rodents by which the binding of SOX10 to RNLTR12-int RNA regulates the transcription of myelin basic protein, encoding a key structural protein of myelin (MBP).   Inhibition of RNLTR12-int expression specifically disrupts the myelination program.  Sequences akin to RNLTR12-int (which we dubbed RetroMyelin) are found in all jawed vertebrates examined but not in lamprey, a jawless fish.  I further demonstrated Retromyelin function in two other vertebrate classes, jawed fish and amphibians.  Phylogenetic analysis indicates that acquisition of these retroviral sequences in different species likely occurred through convergent evolution and were adopted and adapted for myelination, indicating that retroviral endogenization played a key role in the evolutionary emergence of myelin and possibly other coordinated genetic programs.

Ghosh, T et al. (2024).  A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression.  Cell 187:814-830.

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