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Single-Stranded Condensation Stochastically Blocks G-Quadruplex Assembly in Human Telomeric RNA

Single-Stranded Condensation Stochastically Blocks G-Quadruplex Assembly in Human Telomeric RNA

Authors :
Irene de Bustamante Gutiérrez
J. Ricardo Arias-Gonzalez
Carlos González
Sara de Lorenzo
Alfredo Villasante
Miguel Garavís
Source :
Repositorio Institucional del Instituto Madrileño de Estudios Avanzados en Nanociencia, instname, RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Publication Year :
2018
Publisher :
American Chemical Society (ACS), 2018.

Abstract

[EN] TERRA is an RNA molecule transcribed from human subtelomeric regions toward chromosome ends potentially involved in regulation of heterochromatin stability, semiconservative replication, and telomerase inhibition, among others. TERRA contains tandem repeats of the sequence GGGUUA, with a strong tendency to fold into a four-stranded arrangement known as a parallel G-quadruplex. Here, we demonstrate by using single-molecule force spectroscopy that this potential is limited by the inherent capacity of RNA to self-associate randomly and further condense into entropically more favorable structures. We stretched RNA constructions with more than four and less than eight hexanucleotide repeats, thus unable to form several G-quadruplexes in tandem, flanked by non-G-rich overhangs of random sequence by optical tweezers on a one by one basis. We found that condensed RNA stochastically blocks G-quadruplex folding pathways with a near 20% probability, a behavior that is not found in DNA analogous molecules.<br />Dedicated to the memory of Alfredo Villasante. The authors thank E. Poyatos-Racionero for auxiliary experiments. I.G. is supported by Fundacion IMDEA Nanociencia and M.G. by a Juan de la Cierva contract (FJCI-2016-28474). This research received grants from the MINECO (MAT2015-71806-R and BFU2017-89707-P). IMDEA Nanociencia acknowledges support from the "Severo Ochoa" Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686).

Details

ISSN :
19487185 and 20162847
Volume :
9
Database :
OpenAIRE
Journal :
The Journal of Physical Chemistry Letters
Accession number :
edsair.doi.dedup.....901b74df1b50a0ba37be6cfc6d4f71ea
Full Text :
https://doi.org/10.1021/acs.jpclett.8b00722