Co-retained intron retention on single RNA molecules marks fitness-critical genes

Using published nanopore direct RNA sequencing from the SG-NEx consortium across six cancer cell lines, we characterize co-retention: the simultaneous retention of adjacent introns on individual transcript molecules. Where it occurs, co-retention is close to absolute (median phi 0.79). This mechanism is distinct from individual retention caused by weak splice sites. Co-retained introns have adequate splice sites, are enriched for TIA1 and U2AF2 binding, and are separated by short exons. Co-retained genes are enriched for fitness-critical components of the translation and splicing machinery.