RESUMEN
Circular RNAs (circRNAs) encompass a widespread and conserved class of RNAs, which are generated by back-splicing of downstream 5' to upstream 3' splice sites. CircRNAs are tissue-specific and have been implicated in diseases including cancer. They can function as sponges for microRNAs (miRNAs) or RNA binding proteins (RBPs), for example. Moreover, some contain open reading frames (ORFs) and might be translated. The functional relevance of such peptides, however, remains largely elusive. Here, we report that the ORF of circZNF609 is efficiently translated when expressed from a circZNF609 overexpression construct. However, endogenous proteins could not be detected. Moreover, initiation of circZNF609 translation is independent of m6A-generating enzyme METTL3 or RNA sequence elements such as internal ribosome entry sites (IRESs). Surprisingly, a comprehensive mutational analysis revealed that deletion constructs, which are deficient in producing circZNF609, still generate the observed protein products. This suggests that the apparent circZNF609 translation originates from trans-splicing by-products of the overexpression plasmids and underline that circRNA overexpression constructs need to be evaluated carefully, particularly when functional studies are performed.
Asunto(s)
Sitios Internos de Entrada al Ribosoma/genética , Metiltransferasas/genética , Biosíntesis de Proteínas , ARN Circular/genética , Secuencia de Bases/genética , Regulación de la Expresión Génica/genética , Células HEK293 , Humanos , MicroARNs/genética , Sitios de Empalme de ARN/genética , ARN Circular/clasificación , Proteínas de Unión al ARN/genéticaRESUMEN
BACKGROUND: Asymmetry and scar formation of the nipple-areola complex (NAC) after reduction mammoplasty with periareolar suture are common complications and can significantly affect patient satisfaction. OBJECTIVE: The aim of this study was to investigate possible procedure-specific influencing factors on asymmetry and shape disturbances of the nipple-areola complex to optimize postoperative outcome and thus improve patient satisfaction. METHODS: 78 patients were followed-up after a 5-year period as part of a retrospective cohort study. Objective parameters as areolar diameter, symmetry, scar patterns, dimensions of the breast, and anthropometric measurements were recorded. All patients underwent surgery according to an established treatment algorithm depending on the preoperative measurements. Follow up was 1 week, 6 week, 6 months and 3 years postoperatively. RESULTS: The periareolar suture-technique significantly influenced the symmetry and shape of the NAC. Compared to the intraoperative determined diameter and the postoperative diameter, the net-suture technique showed the highest NAC symmetry and minimal divergence. Patients who underwent Hall-Findlay mammoplasty showed significantly higher rates of asymmetry and deformity of the NAC with teardrop formation in comparison to Lejour mammoplasty. Scar formation was affected by periareolar ruffle formation especially after purse string suture. CONCLUSIONS: Regardless of what reduction mammoplasty techniques and periareolar suturing-technique are used, a tension-free suture of the NAC is crucial for shape, symmetry and scar formation. The net suture technique resulted in significantly higher symmetry of the NAC.