Human ARMC6 binds in vitro to both cancer genes and telomeric RNA, favoring G-quadruplex structure recognition.

Autor: Adámik M; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Soldánová Z; Department of Molecular Pharmacy, Faculty of Pharmacy, Masaryk University, Palackého 1/3, 612 42 Brno, Czech Republic., Drotárová M; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Brečková K; Department of Molecular Pharmacy, Faculty of Pharmacy, Masaryk University, Palackého 1/3, 612 42 Brno, Czech Republic., Petr M; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Helma R; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Jenner LP; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Vorlíčková M; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Sýkorová E; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic., Brázdová M; Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Královopolská 135, 612 00 Brno, Czech Republic; Department of Molecular Pharmacy, Faculty of Pharmacy, Masaryk University, Palackého 1/3, 612 42 Brno, Czech Republic. Electronic address: maruska@ibp.cz.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Gene regulatory mechanisms [Biochim Biophys Acta Gene Regul Mech] 2024 Sep; Vol. 1867 (3), pp. 195050. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1016/j.bbagrm.2024.195050
Abstrakt: Armadillo repeat-containing proteins (ARMCs) are a large family found throughout eukaryotes, which play prominent roles in cell adhesion, signaling and cytoskeletal regulation. The ARMC6 protein is highly conserved in primates, including humans, but to date does not have a clear function beyond initial hints of a link to cancer and telomerase activity. We report here in vitro experiments showing ARMC6 binding to DNA promoter sequences from several cancer-related genes (e.g., EGFR, VEGF and c-MYC), and also to the telomeric RNA repeat (TERRA). ARMC6 binding activity appears to recognize G-quadruplex motifs, which are being increasingly implicated as structure-based protein binding sites in chromosome maintenance and repair. In vivo investigation of ARMC6 function revealed that when this protein is overexpressed in human cell lines, there is different expression of genes connected with oncogenic pathways and those implicated in downstream non-canonical telomerase pathways (e.g., VEGF, hTERT, c-MYC, ESM1, MMP3). ARMC6 is already known to interact with human shelterin protein TRF2 and telomerase. The protein binds G-quadruplex structures and does so preferentially to RNA over DNA. As such, this protein may be an example of how a non-canonical nucleic acid structural motif allows mediation between gene regulation and telomeric chromatin rearrangement pathways.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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