A long-read RNA sequencing and polysome profiling framework reveals transposable element–driven transcript diversity and translational rewiring in glioblastoma [polysome]

TEs can add cryptic splice sites, undergo exonization, and generate gene–TE fusion transcripts, but the combined effects of TEs on RNA processing and translation in glioblastoma stem cells (GSCs) remains incompletely elucidated. We combined long-read RNA sequencing with polysome profiling in four patient-derived GSCs and two neural stem cell (NSC) controls to resolve TE-associated transcript diversity and its relationship to ribosomal engagement.

Across GSCs, we identified 13,421 alternative splicing (AS) events, 3,077 of which contained TEs within 150 bp of splice junctions. AS sites proximal to TEs were associated with increased isoform switching compared to non–TE-associated AS sites (odds ratio 2.9 - 4.3). Moreover, AS isoforms generated from TE-proximal sites were more likely to exhibit altered ribosomal association (odds ratio 2.54).