Implications of differential Transcription Start Site selection on CML and prostate cancer cell protein expression

Surani, AA ORCID: https://orcid.org/0000-0002-5180-9075, Spriggs, KA, Ufer, C, Polytarchou, C ORCID: https://orcid.org/0000-0002-1948-7934 and Montiel-Duarte, C ORCID: https://orcid.org/0000-0002-9144-8809, 2022. Implications of differential Transcription Start Site selection on CML and prostate cancer cell protein expression. iScience: 105519. ISSN 2589-0042

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Abstract

The relevance of minor transcription start sites in broad promoters is not well understood. We have studied AGAP2 expression in prostate cancer and chronic myeloid leukaemia (CML), showing transcription is initiated from alternative transcription start sites (TSSs) within a single TSS cluster, producing cancer-type-specific AGAP2 mRNAs with small differences in their 5' UTR length. Interestingly, in the CML cell lines where the 5’ UTR is longer, AGAP2 protein levels are lower. We demonstrate that the selection of an upstream TSS involved the formation of a G quadruplex in the 5' UTR, decreasing polysome formation. After developing a bioinformatics pipeline to query data from the FANTOM project and the NCl-60 human tumour cell lines screen, we found HK1 expression can also be regulated by the same mechanism. Overall, we present compelling data supporting TSS selection within a TSS cluster play a role on protein expression and should not be ignored.

Item Type:	Journal article
Publication Title:	iScience
Creators:	Surani, A.A., Spriggs, K.A., Ufer, C., Polytarchou, C. and Montiel-Duarte, C.
Publisher:	Elsevier (Cell Press)
Date:	8 November 2022
ISSN:	2589-0042
Identifiers:	Number Type 10.1016/j.isci.2022.105519 DOI 1615698 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	08 Nov 2022 15:48
Last Modified:	08 Nov 2022 15:48
Related URLs:	Publisher
URI:	https://irep.ntu.ac.uk/id/eprint/47355

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