NEUROGENOMICS will be presenting a seminar by Guillermo Parada – Wellcome Sanger Institute
Uncovering alternative splicing patterns of microexons across mouse development and neuronal cell-types

Zoom meeting ID 944 6153 8151
Passcode 858918

In association with Imperial college and UK Dementia Institute.

Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically
regulated set of cassette exons. They have key roles in nervous system development and
function, as evidenced by recent results demonstrating the impact of microexons on
behaviour and cognition. However, microexons are often overlooked due to the
difficulty of detecting them using standard RNA-seq aligners. Thus, we developed
MicroExonator, a novel pipeline for reproducible de novo discovery and quantification
of microexons. We process 289 RNA-seq datasets from eighteen mouse tissues
corresponding to nine embryonic and postnatal stages, providing the most
comprehensive survey of microexons available for mice. We detect 2984 microexons, 332
of which are differentially spliced throughout mouse embryonic brain development,
including 29 that are not present in mouse transcript annotation databases. Unsupervised
clustering of microexons based on their inclusion patterns segregates brain tissues by
developmental time, and further analysis suggests a key function for microexons in axon
growth and synapse formation. Finally, we analyse single-cell RNA-seq data from the
mouse visual cortex, and for the first time, we report differential inclusion between
neuronal subpopulations, suggesting that some microexons could be cell type-specific.
MicroExonator facilitates the investigation of microexons in transcriptome studies,
particularly when analysing large volumes of data. As a proof of principle, we use
MicroExonator to analyse a large collection of both mouse bulk and single-cell RNA-seq
datasets. The analyses enabled the discovery of previously uncharacterized microexons,
and our study provides a comprehensive microexon inclusion catalogue during mouse
development and cortical cell-types.