Killam Seminar Series: Molecular Biology of the Fragile X Syndrome

Event

Speaker: Joel Richter, Ph.D.

Arthur F. Koskinas Professor in Neuroscience, University of Massachusetts Medical School, USA

Registration: available now on Eventbrite

Livestreaming via Vimeo: Vimeo

Abstract: Silencing of FMR1 and loss of its gene product, FMRP, results in fragile X syndrome (FXS). FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1-deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wild-type tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes, and its loss results in decline of ribosome stalling on specific mRNAs. One such mRNA encodes SETD2, a lysine methyltransferase that catalyzes H3K36me3. Chromatin immunoprecipitation sequencing (ChIP-seq) demonstrates that loss of FMRP alters the deployment of this histone mark. H3K36me3 is associated with alternative pre-RNA processing, which we find occurs in an FMRP-dependent manner on transcripts linked to neural function and autism spectrum disorders.


The Killam Seminar Series at The Neuro

Supported by the generosity of the Killam Trusts, The Neuro’s Killam Seminar series hosts outstanding guest speakers whose research is of interest to the scientific community at The Neuro and McGill University.


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Contact Information

Contact: 
Sasha Kelly
Organization: 
Montreal Neurological Institute-Hospital
Email: 
sasha.kelly [at] mcgill.ca

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The Neuro is a McGill research and teaching institute; delivering high quality patient care, as part of the Neuroscience Mission of the McGill University Health Centre. We are proud to be a Killam Institution, supported by the Killam Trusts.

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