The role of G-Quadruplex DNA in Paraspeckle formation in cancer

Uditi Bhatt, Amy L. Kretzmann, Aurore Guédin, Arnold Ou, Simon Kobelke, Charles S. Bond, Cameron W. Evans, Laurence H. Hurley, Jean-Louis Mergny, Killugudi Swaminatha Iyer, Archa H. Fox, Nicole M. Smith

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Paraspeckles are RNA–protein structures within the nucleus of mammalian cells, capable of orchestrating various biochemical processes. An overexpression of the architectural component of paraspeckles, a long non-coding RNA called NEAT1 (Nuclear Enriched Abundant Transcript 1), has been linked to a variety of cancers and is often associated with poor patient prognosis. Thus, there is an accumulating interest in the role of paraspeckles in carcinogenesis, however there is a limited understanding of how NEAT1 expression is regulated. Here, we demonstrate that both nuclear G-quadruplex (G4) and paraspeckle formation are significantly increased in a human breast cancer cell line compared to non-tumorigenic breast cells. Moreover, we identified and characterized G4-forming sequences within the NEAT1 promoter and demonstrate stabilization of G4 DNA with a G4-stabilizing small molecule results in a significant alteration in both paraspeckle formation and NEAT1 expression. This G4-mediated alteration of NEAT1 at both the transcriptional and post-transcriptional levels was evident in U2OS osteosarcoma cells, MCF-7 breast adenocarcinoma and MDA-MB-231 triple negative breast cancer cells.
Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalBiochimie
Volume190
DOIs
Publication statusPublished - Nov 2021

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