Evaluation of i-motif formation in the serotonin transporter-linked polymorphic region.pdf (1.21 MB)
Download fileEvaluation of i-Motif Formation in the Serotonin Transporter-Linked Polymorphic Region
journal contribution
posted on 2022-01-19, 20:05 authored by Bryony Thorne, Albertus EllenbroekAlbertus Ellenbroek, Darren DayDarren DayNeuropsychiatric disorders such as major depressive disorder (MDD) arise from a complex set of genetic and environmental factors. The serotonin transporter (SERT) is a key regulator of synaptic serotonin (5-HT), and its inhibition is an important pharmacological target for treating MDD. The SERT-linked polymorphic region (5-HTTLPR) contains two major variants (short and long) that have been implicated in modulating susceptibility to MDD by altering the level of expression of SERT. Both variants contain C-rich repeats that conform to consensus i-motif folding sequences. i-Motifs are quadruplex DNA structures that have been proposed to have a role in transcription regulation. With spectroscopic techniques, we demonstrate that both alleles are able to form i-motifs at acidic pH, and at neutral pH under conditions of molecular crowding. This highlights the potential for i-motif formation to contribute to transcriptional regulation of the serotonin transporter, with a potential role in the pathophysiology of neuropsychiatric disorders.
History
Preferred citation
Thorne, B. N., Ellenbroek, B. A. & Day, D. J. (2021). Evaluation of i-Motif Formation in the Serotonin Transporter-Linked Polymorphic Region. ChemBioChem, 22(2), 349-353. https://doi.org/10.1002/cbic.202000513Publisher DOI
Journal title
ChemBioChemVolume
22Issue
2Publication date
2021-01-15Pagination
349-353Publisher
WileyPublication status
PublishedOnline publication date
2020-10-16ISSN
1439-4227eISSN
1439-7633Language
enUsage metrics
Categories
Keywords
gene expressioni-motifmajor depressive disordernucleic acidsserotonin transporterG-QuadruplexesHydrogen-Ion ConcentrationOligonucleotidesSerotonin Plasma Membrane Transport ProteinsMental HealthNeurosciencesGeneticsBrain DisordersDepression2.1 Biological and endogenous factorsMental healthOrganic ChemistryMedicinal and Biomolecular Chemistry not elsewhere classifiedBiochemistry and Cell Biology not elsewhere classified