Leveraging short and long-read sequencing to comprehensively characterize alternatively polyadenylated and alternatively spliced transcripts

In mantle cell lymphoma (MCL), SOX11 and ATM express transcripts with short 3'UTRs, and canonical plus non-canonical polyadenylation signals are used for 3' end formation.

• Why it matters: Alternative splicing and alternative polyadenylation can reshape transcript localization, stability, and translation, but the full transcript repertoire in MCL under disease states is not well defined.
• What they did: Using short-read and long-read sequencing in MCL, the study assessed 3'UTR length patterns and PAS usage, then experimentally verified the PASs used by specific transcripts and classified splice variants.
• The result: Short-read data did not show widespread global 3'UTR shortening in MCL, while long-read integration enabled identification of alternatively spliced variants (including PTEN and EZH2) and protein-level validation of GLS1 with GLS1 inhibitors.

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