Local translation of mRNA underpins the development and function of?cell compartments located far from the soma, such as?neuronal axons and dendrites. To ensure proper local translation, local transcriptomic landscapes require tight regulation. Disruption of such regulation directly impacts on?local translation and subsequently the health and function of axons and dendrites.
My research is focused on better understanding localised RNA regulation in neurons; specifically?the role/s of intron retention. Introns are the 'non-coding' sequences classically spliced from pre-mRNAs following transcription in the nucleus. Intron-retaining transcripts are those in which one or multiple introns are not spliced.?Recently, we identified?that many intron-retaining transcripts are enriched in neuronal axons and dendrites compared to the soma. Very little is known about the role/s of such transcripts, and whether in this context?intronic sequence?encodes protein.
My work also studies how localised RNA?regulation is perturbed in neurodegeneration. SFPQ is an RNA-binding protein that predominantly functions as a splicing factor, but which also locates to axons and dendrites and regulates their?local?transcriptomes. SFPQ misregulation is a hallmark of Amyotrophic lateral sclerosis (ALS) regardless of the genetic cause of disease, suggesting that it may be a central player in pathogenesis.
