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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
- 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).
- Subjects :
- 0301 basic medicine
Semiconservative replication
Heterochromatin
Optical tweezers
Nucleic Acid Denaturation
G-quadruplex
03 medical and health sciences
chemistry.chemical_compound
Tandem repeat
Humans
General Materials Science
Physical and Theoretical Chemistry
Base Sequence
Force spectroscopy
RNA
TERRA
Single-molecule
Folding
DNA
Telomere
Subtelomere
G-Quadruplexes
030104 developmental biology
chemistry
FISICA APLICADA
Biophysics
Subjects
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