RESUMEN
NEAT1 RNA, a highly abundant 4 kb ncRNA, is retained in nuclei in approximately 10 to 20 large foci that we show are completely coincident with paraspeckles, nuclear domains implicated in mRNA nuclear retention. Depletion of NEAT1 RNA via RNAi eradicates paraspeckles, suggesting that it controls sequestration of the paraspeckle proteins PSP1 and p54, factors linked to A-I editing. Unlike overexpression of PSP1, NEAT1 overexpression increases paraspeckle number, and paraspeckles emanate exclusively from the NEAT1 transcription site. The PSP-1 RNA binding domain is required for its colocalization with NEAT1 RNA in paraspeckles, and biochemical analyses support that NEAT1 RNA binds with paraspeckle proteins. Unlike other nuclear-retained RNAs, NEAT1 RNA is not A-I edited, consistent with a structural role in paraspeckles. Collectively, results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain.
Asunto(s)
Núcleo Celular/metabolismo , Cuerpos de Inclusión Intranucleares/química , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , ARN Nuclear Pequeño/fisiología , Animales , Células Cultivadas , Proteínas de Cloroplastos , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Inmunoprecipitación , Ratones , Interferencia de ARN , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
The past few years has seen a resurgence of syphilis. It is predominantly associated within men who have sex with men and also within heterosexual Indigenous Australians. Possessing the ability to mimic a variety of ocular diseases, it typically manifests as uveitis, although it can affect any structure within the eye. Thus, a high degree of clinical suspicion by ophthalmologists is required to prevent disease progression and ocular morbidity. Patients require prolonged antibiotic treatment with intravenous benzylpenicillin and outpatient monitoring to successfully resolve the infection. We describe a case series of ocular syphilis presentations in Queensland, Australia.