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Telomere Function and the G-Quadruplex Formation are Regulated by hnRNP U

1 and 2,3,*
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Fukuoka 807-8555, Japan
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden
Oncology Laboratory, University of Gothenburg, Sahlgrenska Hospital, Gula stråket 8, SE-41345 Gothenburg, Sweden
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 390;
Received: 13 March 2019 / Revised: 22 April 2019 / Accepted: 25 April 2019 / Published: 28 April 2019
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
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We examine the role of the heterogenous ribonucleoprotein U (hnRNP U) as a G-quadruplex binding protein in human cell lines. Hypothesizing that hnRNP U is associated with telomeres, we investigate what other telomere-related functions it may have. Telomeric G-quadruplexes have been fully characterized in vitro, but until now no clear evidence of their function or in vivo interactions with proteins has been revealed in mammalian cells. Techniques used were immunoprecipitation, DNA pull-down, binding assay, and Western blots. We identified hnRNP U as a G-quadruplex binding protein. Immunoprecipitations disclosed that endogenous hnRNP U associates with telomeres, and DNA pull-downs showed that the hnRNP U C-terminus specifically binds telomeric G-quadruplexes. We have compared the effect of telomere repeat containing RNA (TERRA) on binding between hnRNP U and telomeric (Tel) or single- stranded Tel (ssTel) oligonucleotides and found that ssTel binds stronger to TERRA than to Tel. We also show that hnRNP U prevents replication protein A (RPA) accumulation at telomeres, and the recognition of telomeric ends by hnRNP suggests that a G-quadruplex promoting protein regulates its accessibility. Thus, hnRNP U-mediated formation has important functions for telomere biology. View Full-Text
Keywords: telomeres; hnRNP U; G-quadruplex; ssTel-oligonucleotide; Tel-oligonucleotide; RPA telomeres; hnRNP U; G-quadruplex; ssTel-oligonucleotide; Tel-oligonucleotide; RPA

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Izumi, H.; Funa, K. Telomere Function and the G-Quadruplex Formation are Regulated by hnRNP U. Cells 2019, 8, 390.

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