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294: Alternative splicing, exonization and lineage-specific isoforms: PTBP1, MAPT and TE-derived exons in mammalian evolution
Hunter CE et al., The EMBO Journal - Review shows how alternative splicing, via TE exonization and cis-regulatory changes and revealed by long-read RNA-seq, reshapes gene regulation and drives phenotypic evolution in mammals.
Study Highlights:
This review synthesizes comparative transcriptomic studies across multicellular eukaryotes with emphasis on vertebrates and mammals. It highlights methods including short- and long-read RNA-seq, single-cell transcriptomics, and MS proteomics to map isoform diversity. The authors emphasize that lineage-specific AS is often driven by cis-regulatory changes and exonization of transposable elements, with trans-factor innovations (e.g., SRRM3/4, PTBP1 isoforms) modulating microexons and isoform ratios. Functional examples linking AS to phenotypes include an Alu-derived IFNAR2 decoy receptor reducing JAK/STAT signaling, TNNI3 exon3 loss or skipping associated with extreme heart rates, and hominoid shifts in MAPT exon10 splicing altering tau isoform proportion.
Conclusion:
Alternative splicing, shaped largely by cis-sequence changes and TE exonization and illuminated by long-read and single-cell transcriptomics, is a flexible evolutionary mechanism that can produce lineage-specific regulatory and phenotypic innovations.
Music:
Enjoy the music based on this article at the end of the episode.
Reference:
Hunter CE, Xing Y. The splice of life: how alternative splicing shapes regulatory and phenotypic evolution. The EMBO Journal. 2026. https://doi.org/10.1038/s44318-025-00666-z
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/
Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
Official website https://basebybase.com
On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.
Episode link: https://basebybase.com/episodes/alternative-splicing-exonization-evolution
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By Gustavo BarraHunter CE et al., The EMBO Journal - Review shows how alternative splicing, via TE exonization and cis-regulatory changes and revealed by long-read RNA-seq, reshapes gene regulation and drives phenotypic evolution in mammals.
Study Highlights:
This review synthesizes comparative transcriptomic studies across multicellular eukaryotes with emphasis on vertebrates and mammals. It highlights methods including short- and long-read RNA-seq, single-cell transcriptomics, and MS proteomics to map isoform diversity. The authors emphasize that lineage-specific AS is often driven by cis-regulatory changes and exonization of transposable elements, with trans-factor innovations (e.g., SRRM3/4, PTBP1 isoforms) modulating microexons and isoform ratios. Functional examples linking AS to phenotypes include an Alu-derived IFNAR2 decoy receptor reducing JAK/STAT signaling, TNNI3 exon3 loss or skipping associated with extreme heart rates, and hominoid shifts in MAPT exon10 splicing altering tau isoform proportion.
Conclusion:
Alternative splicing, shaped largely by cis-sequence changes and TE exonization and illuminated by long-read and single-cell transcriptomics, is a flexible evolutionary mechanism that can produce lineage-specific regulatory and phenotypic innovations.
Music:
Enjoy the music based on this article at the end of the episode.
Reference:
Hunter CE, Xing Y. The splice of life: how alternative splicing shapes regulatory and phenotypic evolution. The EMBO Journal. 2026. https://doi.org/10.1038/s44318-025-00666-z
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/
Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00
Official website https://basebybase.com
On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.
Episode link: https://basebybase.com/episodes/alternative-splicing-exonization-evolution