title: RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the Replication of Rhinovirus, Influenza A Virus, and Dengue Virus.
abstract: Human rhinovirus (HRV) causes upper respiratory infections and asthma exacerbations. We screened multiple orthologous RNAi reagents and identified host proteins that modulate HRV replication. Here, we show that RNASEK, a transmembrane protein, was needed for the replication of HRV, influenza A virus, and dengue virus. RNASEK localizes to the cell surface and endosomal pathway and closely associates with the vacuolar ATPase (V-ATPase) proton pump. RNASEK is required for endocytosis, and its depletion produces enlarged clathrin-coated pits (CCPs) at the cell surface. These enlarged CCPs contain endocytic cargo and are bound by the scissioning GTPase, DNM2. Loss of RNASEK alters the localization of multiple V-ATPase subunits and lowers the levels of the ATP6AP1 subunit. Together, our results show that RNASEK closely associates with the V-ATPase and is required for its function; its loss prevents the early events of endocytosis and the replication of multiple pathogenic viruses.
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Perreira
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Aker
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: George
authors.initials: G
authors.lastname: Savidis
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Chin
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: McDougall
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Portmann
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Meraner
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Miles C
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Motiur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Baker
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Annick
authors.initials: A
authors.lastname: Gauthier
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Franti
authors.affiliation: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA. Electronic address: abraham.brass@umassmed.edu.
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Brass
mesh_terms: D003716:Dengue Virus / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D012229:Rhinovirus / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D004722:Endoribonucleases; C065559:ribonuclease K; D025262:Vacuolar Proton-Translocating ATPases