Project : Ultra-long sequencing to detect cancer-associated intron retention

Intron retention (IR) occurs when an intron is included in a mature mRNA.

Previously regarded as a by-product of faulty splicing, transcripts with retained introns are often rapidly degraded by a surveillance mechanism called nonsense-mediated decay (NMD).

We discovered that numerous cell types make use of this mechanism by increasing the amount of transcripts with retained introns for degradation in granulopoiesis (Cell, 2013), pluripotent stem cells (Nature, 2014) and erythrocyte differentiation (Blood, 2016).

IR was recently found to have a major role in modulating tumour suppressor genes in hundreds of different cancers (Nature Genetics, 2015).

However, because IR could not previously be correctly identified, numerous studies have overlooked potential biomarkers and therapeutic targets linked to this novel type of gene regulation.

In this project we will combine new long RNA sequencing with classical Illumina sequencing to define IR with unprecedented accuracy. This will enable us to define IR features that contribute to normal development and disease.