title: Minute Virus of Canines NP1 Protein Governs the Expression of a Subset of Essential Nonstructural Proteins via Its Role in RNA Processing.
abstract: Parvoviruses use a variety of means to control the expression of their compact genomes. The bocaparvovirus minute virus of canines (MVC) encodes a small, genus-specific protein, NP1, which governs access to the viral capsid gene via its role in alternative polyadenylation and alternative splicing of the single MVC pre-mRNA. In addition to NP1, MVC encodes five additional nonstructural proteins (NS) that share an initiation codon at the left end of the genome and which are individually encoded by alternative multiply spliced mRNAs. We found that three of these proteins were encoded by mRNAs that excise the NP1-regulated MVC intron immediately upstream of the internal polyadenylation site, (pA)p, and that generation of these proteins was thus regulated by NP1. Splicing of their progenitor mRNAs joined the amino termini of these proteins to the NP1 open reading frame, and splice site mutations that prevented their expression inhibited virus replication in a host cell-dependent manner. Thus, in addition to controlling capsid gene access, NP1 also controls the expression of three of the five identified NS proteins via its role in governing MVC pre-mRNA splicing.IMPORTANCETheParvovirinaeare small nonenveloped icosahedral viruses that are important pathogens in many animal species, including humans. Minute virus of canine (MVC) is an autonomous parvovirus in the genusBocaparvovirusIt has a single promoter that generates a single pre-mRNA. NP1, a small genus-specific MVC protein, participates in the processing of this pre-mRNA and so controls capsid gene access via its role in alternative internal polyadenylation and splicing. We show that NP1 also controls the expression of three of the five identified NS proteins via its role in governing MVC pre-mRNA splicing. These NS proteins together are required for virus replication in a host cell-dependent manner.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri, USA.
authors.forename: Olufemi O
authors.initials: OO
authors.lastname: Fasina
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stupps
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri, USA.
authors.forename: Wanda
authors.initials: W
authors.lastname: Figueroa-Cuilan
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri, USA pinteld@missouri.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pintel
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D052660:Bocavirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics; D018387:Codon, Initiator; D004285:Dogs; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D007438:Introns; D061985:Madin Darby Canine Kidney Cells; D026723:Polyadenylation; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000502:physiology*; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D018387:Codon, Initiator; D012322:RNA Precursors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins
keywords: gene expression; parvovirus