Malcolm, Jodie R, Leese, Natasha K, Lamond-Warner, Philippa I et al. (2 more authors) (2022) Widespread association of ERα with RMRP and tRNA genes in MCF-7 cells and breast cancers. Gene. 146280. ISSN 0378-1119
Abstract
tRNA gene transcription by RNA polymerase III (Pol III) is a tightly regulated process, but dysregulated Pol III transcription is widely observed in cancers. Approximately 75% of all breast cancers are positive for expression of Estrogen Receptor alpha (ERα), which acts as a key driver of disease. MCF-7 cells rapidly upregulate tRNA gene transcription in response to estrogen and ChIP-PCR demonstrated ERα enrichment at tRNALeu and 5S rRNA genes in this breast cancer cell line. While these data implicate the ERα as a Pol III transcriptional regulator, how widespread this regulation is across the 631 tRNA genes has yet to be revealed. Through analyses of ERα ChIP-seq datasets, we show that ERα interacts with hundreds of tRNA genes, not only in MCF-7 cells, but also in primary human breast tumours and distant metastases. The extent of ERα association with tRNA genes varies between breast cancer cell lines and does not correlate with levels of ERα binding to its canonical target gene GREB1. Amongst other Pol III-transcribed genes, ERα is consistently enriched at the long non-coding RNA gene RMRP, a positive regulator of cell cycle progression that is subject to focal amplification in tumours. Another Pol III template targeted by ERα is the RN7SL1 gene, which is strongly implicated in breast cancer pathology by inducing inflammatory responses in tumours. Our data indicate that Pol III-transcribed non-coding genes should be added to the list of ERα targets in breast cancer.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2022 The Authors. |
Keywords: | Breast Neoplasms/genetics,Cell Cycle,Estrogen Receptor alpha/metabolism,Female,Humans,MCF-7 Cells,Neoplasm Metastasis,RNA, Long Noncoding/genetics,RNA, Ribosomal, 5S/genetics,RNA, Small Cytoplasmic/genetics,RNA, Transfer/genetics,RNA, Transfer, Leu/genetics,Signal Recognition Particle/genetics |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 06 Jul 2022 11:40 |
Last Modified: | 24 Oct 2024 00:16 |
Published Version: | https://doi.org/10.1016/j.gene.2022.146280 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.gene.2022.146280 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:188794 |
Download
Filename: 1_s2.0_S0378111922000993_main.pdf
Description: 1-s2.0-S0378111922000993-main
Licence: CC-BY 2.5