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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
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).
Thoreen, C. C. et al. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109–113 (2012). A primary paper establishing the role of the 5′TOP motif in regulating differential post-transcriptional processing.
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.
van Riggelen, J., Yetil, A. & Felsher, D. W. MYC as a regulator of ribosome biogenesis and protein synthesis. Nat. Rev. Cancer 10, 301–309 (2010). A review article discussing the role of Myc in transcriptional regulation of translation machinery.
Haberle, V. et al. Two independent transcription initiation codes overlap on vertebrate core promoters. Nature 507, 381–385 (2014). A primary paper that presents switching in core promoter usage in zebrafish development.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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).
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41594-023-01157-7
