Event Details

Wednesday, 19 October 2016
12:00 pm - 1:00 pm
QBI Level 7 Auditorium
UQ Location:
Queensland Brain Institute (St Lucia)
Event category(s):

Event Contact

Ms Deirdre Wilson
334 66300
Org. Unit:
Queensland Brain Institute

Event Description

Full Description:
Dr Jocelyn Widagdo, Queensland Brain Institute, University of Queensland

Title: Activity-dependent RNA methylation in learning and memory

Abstract: The regulation of RNA is fundamental to cellular biology. The entire lifespan of RNA molecules, from their initial synthesis in the nucleus to translation and/or degradation in the cytoplasm, is carefully controlled by multiple factors to ensure their proper structure and function. Recent studies in the field of RNA post-transcriptional modification (also known as the epitranscriptome) have revealed its dynamic regulation and versatile roles in controlling the structure, function and stability of RNA, which are essential for many cellular and biological processes. One such evolutionarily conserved mechanism is the methylation of adenosine, N6-methyladenosine (m6A). Known as the most prevalent internal modification on eukaryotic RNA, m6A is catalysed by an RNA methyltransferase complex and is reversed by the m6A demethylating enzyme, namely, the fat mass- and obesity-associated protein (FTO). In brain, the level of m6A is developmentally upregulated and peaks in adulthood, suggestive of its significant roles in adult brain function and plasticity. However, it has not been determined whether m6A is dynamically regulated by experience. Using an antibody-based m6A capture technique followed by high throughput RNA sequencing (MeRIP-seq), we showed that m6A transcriptomic landscape was dynamically regulated in the mouse medial prefrontal cortex following behavioural training. Transcriptome-wide profiling of m6A revealed learning-specific patterns of RNA methylation, with the highest enrichment positioned near the stop codon. In primary cortical neurons, in vitro, modulation of m6A by the RNA demethylase FTO influenced learning- and plasticity-related mRNA stability. Targeted knockdown of FTO in the mouse medial prefrontal cortex led to enhanced consolidation of cued fear memory, without affecting basal anxiety level. Taken together, these findings provide the first demonstration of the role of epitranscriptome in learning and memory.

Directions to UQ

Google Map:
To St Lucia Campus, UQ Ipswich, and UQ Gatton.

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