The abstract is read at the publisher; the summary is JClub's.
In mouse brain, liver, and adipose during natural aging and Ercc1 knockout, 36.5–42.6% of age-linked isoform switches alter predicted coding sequence, indicating widespread regulatory DTU.
- Why it matters: Aging-related dysregulated splicing can reshape regulatory programs and proteome-linked outputs, but tissue-specific isoform switch patterns and their structural implications remain unclear.
- What they did: They mapped differential transcript usage and isoform switches across three tissues in natural aging and Ercc1 knockout mice, then applied functional annotation and structural/ensemble modeling, including BioEMU with a seven-fold eligibility cascade.
- The result: Most switches appear regulatory: 31.2–36.5% involve non-coding alternative arms and 11–18% encode an identical protein; brain shows 3'-UTR lengthening while adipose shortens, and modeling supports conformational-ensemble targets for a minority of switches.
The findingWhy it mattersWhat they didThe result
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