We describe how transcription start site (TSS) choice of thousands of genes results in transcript isoforms with potential for distinct post-transcriptional regulation affecting translation and cell behavior. We show that dynamic switching between initiation sites defines cancer proliferation, differentiation and treatment response, indicating start site determination as a potential diagnostic tool.
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References
Nepal, C. et al. Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing. Nat. Commun. 11, 168 (2020). A primary paper that presents dual initiator promoters for the first time (to our knowledge).
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Fonseca, B. D. et al. La-related protein 1 (LARP1) represses terminal oligopyrimidine (TOP) mRNA translation downstream of mTOR complex 1 (mTORC1). J. Biol. Chem. 290, 15996–16020 (2015). A primary paper establishing the role of mTORC1 in regulating differential post-transcriptional processing of 5′TOP transcripts.
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This is a summary of: Wragg, J. W. et al. Intra-promoter switch of transcription initiation sites in proliferation signaling-dependent RNA metabolism. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-023-01156-8 (2023).
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Transcription start site choice diversifies mRNA isoforms and defines cancer cell behavior. Nat Struct Mol Biol 30, 1840–1841 (2023). https://doi.org/10.1038/s41594-023-01157-7
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DOI: https://doi.org/10.1038/s41594-023-01157-7