RESUMO
Stress triggers the formation of two distinct cytoplasmic biomolecular condensates: stress granules (SGs) and processing bodies (PBs), both of which may contribute to stress-responsive translation regulation. Though PBs can be present constitutively, stress can increase their number and size and lead to their interaction with stress-induced SGs. The mechanism of such interaction, however, is largely unknown. Formation of canonical SGs requires the RNA binding protein Ubiquitin-Associated Protein 2-Like (UBAP2L), which is a central SG node protein in the RNA-protein interaction network of SGs and PBs. UBAP2L binds to the essential SG and PB proteins G3BP and DDX6, respectively. Research on UBAP2L has mostly focused on its role in SGs, but not its connection to PBs. We find that UBAP2L is not solely an SG protein but also localizes to PBs in certain conditions, contributes to PB biogenesis and SG-PB interactions, and can nucleate hybrid granules containing SG and PB components in cells. These findings inform a new model for SG and PB formation in the context of UBAP2L's role.
Assuntos
RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , Humanos , Grânulos de Estresse/metabolismo , Grânulos de Estresse/genética , RNA Helicases/metabolismo , RNA Helicases/genética , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Corpos de Processamento/metabolismo , Corpos de Processamento/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Grânulos Citoplasmáticos/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Células HeLa , DNA Helicases/metabolismo , DNA Helicases/genética , Células HEK293 , Ligação Proteica , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Proteínas Proto-OncogênicasRESUMO
The patient is an 82-year-old male with a past medical history of aortic valve replacement who presented to the emergency department after a fall. He developed atrial fibrillation with a rapid ventricular response and non-ST-segment-elevation myocardial infarction, leading to hospitalization. During hospital admission, the patient complained of midline thoracic back pain, and an extensive evaluation for this complaint revealed discitis and osteomyelitis with epidural abscess near the T7 and T8 vertebrae that did not result in neurological deficits and required no surgical intervention. A total of 2 blood cultures were reported positive for Actinomyces naeslundii, Streptococcus mitis, Streptococcus oralis, and Abiotrophia defectiva. A transesophageal echocardiogram showed a small vegetation on the aortic prosthetic valve with probable small vegetation on the mitral valve. He was prescribed ceftriaxone intravenously for 12 weeks, followed by amoxicillin 2 g orally twice a day for at least 12 months. A. naeslundii is not commonly known to cause infective endocarditis, whereas S. mitis, S. oralis, and A. defectiva have been reported to do so. One previous case of A. naeslundii was reported to cause prosthetic valve endocarditis as a single infectious agent. To our knowledge, this is the first case report for A. naeslundii as part of multimicrobial bacteremia leading to endocarditis, discitis, and osteomyelitis.
