Journal of Clinical Pathology and Laboratory Medicine

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
Reach Us +1 (202) 780-3397

Short Communication - Journal of Clinical Pathology and Laboratory Medicine (2021) Volume 3, Issue 3

New insights on non-canonical DNA structures: G-Quadruplex folding of RPGR exon ORF15 might impair photoreceptor vesicular trafficking and ciliogenesis

During last years it has becoming evident that non-Watson–Crick base pairing, resulting in the assembly of alternative DNA secondary structures, also occurs in the genome. Such noncanonical structures, called non-B form DNA, include the G-quadruplexes, stacked nucleic acid structures that form within G-rich DNA or RNA sequences. Dysregulation of DNA-G4 is associated with human disorders, including neurological dysfunction and accelerated ageing, even if its role in neurophysiology/neuropathology has not yet been fully elucidated. We present results coming from our recent experiments on X-linked retinitis pigmentosa (OMIM 26800), a group of hereditary disorders that can lead to blindness because of photoreceptor degenerations. The most frequently mutated Xlinked retinitis pigmentosa genes is RPGR (RP3), and codes for a protein with a series of six RCC1-like domains (RLDs), involved in ciliogenesis, microtubule organization and regulation of transport in primary cilia. RPGR presents a splicing variant, called exon ORF15, which constitutes a mutational hot spot in a huge number of patients. The most challenge peculiarity of exon ORF15 is its repetitive nature, particularly of guanine (G)-rich sequences, that makes it very difficult to screen. Thus, we investigated the possible molecular causes that determine such difficulties by a multiple in-silico approach, evaluating the possibility that, due to its nature, exon ORF15 could show a G-quadruplex structure. All exploited algorithms confirmed the possibility that several G-quadruplex could be folded in RPGR exon ORF15, providing new insights towards a better sequencing approach to RPGR screening and Xlinked retinitis pigmentosa diagnosis.

Author(s): Luigi DONATO

Abstract PDF

Get the App