RESUMEN
The G-quadruplexes form highly stable nucleic acid structures, which are implicated in various biological processes in both DNA and RNA. Although DNA G-quadruplexes have been studied in great detail, biological roles of RNA G-quadruplexes have received less attention. Here, a screening of a chemical library permitted identification of a small-molecule tool that binds selectively to RNA G-quadruplex structures. The polyaromatic molecule, RGB-1, stabilizes RNA G-quadruplex, but not DNA versions or other RNA structures. RGB-1 intensified the G-quadruplex-mediated inhibition of RNA translation in mammalian cells, decreased expression of the NRAS proto-oncogene in breast cancer cells, and permitted identification of a novel sequence that forms G-quadruplex in NRAS mRNA. RGB-1 may serve as a unique tool for understanding cellular roles of RNA G-quadruplex structures.
Asunto(s)
G-Cuádruplex , Biosíntesis de Proteínas/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Evaluación Preclínica de Medicamentos , ARN Mensajero/química , ARN Mensajero/genéticaRESUMEN
An 82-year-old man experienced sudden-onset left shoulder pain and hemiparesis, which subsided on the third day. MRI revealed an ischaemic lesion at the C3-4 level together with disk herniation and cord compression from C3/4 to C6/7. On the fourth day, however, similar symptoms recurred when straining during defecation, and then progressed in a fluctuating manner and finally resulted in quadriparesis and respiratory impairment. A follow-up MRI showed fresh infarction of the anterior spinal artery (ASA) territory extending from C2 to C5. Straining during defecation may have induced the second exacerbation by elevating the venous pressure in the craniospinal axis and intervertebral disc pressure and causing minor damage and intraluminal thrombus in the ASA.