RNA splicing is a critical step in gene expression in which non‐protein coding introns are removed from newly transcribed RNA. RNA splicing is carried out by the dynamic spliceosome and may occur directly after or concurrent with transcription, suggesting a close relationship between these processes. Indeed, there is mounting evidence that transcription and RNA splicing are coordinated, however the mechanistic details underlying this coordination are still lacking. The NuA4 protein complex is a histone acetylation transferase (HAT) with known functions in transcription. NuA4 works in conjunction with Swr1, an ATP‐dependent chromatin remodeling enzyme. Histone acetylation by NuA4 recruits Swr1, which subsequently exchanges H2A for the variant histone H2AZ to activate transcription. Together, these complexes regulate the transcription of ribosomal protein genes (RPGs), which comprise a substantial proportion of the genes that contain introns in Saccharomyces cerevisiae. Thus, NuA4 and Swr1 are perfectly positioned to link transcription and RNA splicing. We identified genetic interactions between genes encoding spliceosome proteins and genes encoding components of the NuA4 (eaf3Δ, eaf7Δ) and Swr1 complexes (vps72Δ and swr1Δ), as well as HTZ1, which encodes H2AZ. Splicing‐specific microarray analysis and reverse transcription‐PCR studies revealed splicing defects in swr1Δ, eaf7Δ, and htz1Δ. In addition, as predicted by our genetic studies, the splicing defects in strains harboring deletions in splicing proteins were exacerbated by deletion of EAF7, SWR1 or HTZ1. These data support a role for NuA4 and Swr1 in RNA splicing. We are currently using chromatin immunoprecipitation assays to test whether NuA4 and Swr1 increase splicing efficiency by recruiting splicing proteins during transcription. Our preliminary results indicate that splicing factor recruitment is altered in the absence of EAF7. Together, these data support a model in which the NuA4 and Swr1 chromatin modification complexes interact with the splicing machinery to coordinate transcription and splicing.Support or Funding InformationCottrell College Science Award from the Research Corporation for Science Advancement (#20186)
Objective To determine the incidence and significance of asymmetric hypermetabolic laryngeal findings on positron emission tomography–computed tomography (PET-CT) in patients with unilateral true vocal fold (TVF) motion abnormalities. Study Design Retrospective cohort. Setting Single-center tertiary care institution. Subjects and Methods The medical records of patients with unilateral TVF motion abnormalities were reviewed. The incidence of normal and asymmetric hypermetabolic laryngeal findings was calculated in patients who underwent PET-CT and laryngeal examination, operative laryngoscopy with biopsy, or injection medialization laryngoplasty. Results A total of 135 patients with unilateral TVF motion abnormalities underwent PET-CT. After exclusion of patients who completed new or surveillance imaging for a laryngeal neoplasm (n = 27), asymmetric hypermetabolic findings in the larynx were noted in 21 (19%) cases: 13 (12%) on the contralateral side of the impaired TVF, 8 (7%) on the ipsilateral side. Two (25%) patients with ipsilateral hypermetabolism had concerning subsequent fiberoptic laryngeal examinations prompting operative biopsy. There was no evidence of inflammatory or neoplastic disease in all patients with contralateral hypermetabolic findings. Fifteen patients completed PET-CT scans after injection medialization procedures; 6 (40%) displayed avidity ipsilateral to the side of the injection. The median time from injection to scan was 27 days, as opposed to 193 days in the unremarkable scans ( P = .011). Conclusion Contralateral hypermetabolism in patients with unilateral TVF motion abnormalities may represent a false-positive finding. Ipsilateral hypermetabolic uptake without recent fold instrumentation warrants prompt diagnostic evaluation.
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