title: The adenovirus L4-22K protein regulates transcription and RNA splicing via a sequence-specific single-stranded RNA binding.
abstract: The adenovirus L4-22K protein both activates and suppresses transcription from the adenovirus major late promoter (MLP) by binding to DNA elements located downstream of the MLP transcriptional start site: the so-called DE element (positive) and the R1 region (negative). Here we show that L4-22K preferentially binds to the RNA form of the R1 region, both to the double-stranded RNA and the single-stranded RNA of the same polarity as the nascent MLP transcript. Further, L4-22K binds to a 5΄-CAAA-3΄ motif in the single-stranded RNA, which is identical to the sequence motif characterized for L4-22K DNA binding. L4-22K binding to single-stranded RNA results in an enhancement of U1 snRNA recruitment to the major late first leader 5΄ splice site. This increase in U1 snRNA binding results in a suppression of MLP transcription and a concurrent stimulation of major late first intron splicing.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden.
authors.forename: Susan
authors.initials: S
authors.lastname: Lan
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden.
authors.forename: Wael
authors.initials: W
authors.lastname: Kamel
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden.
authors.forename: Tanel
authors.initials: T
authors.lastname: Punga
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Akusjärvi
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D023061:Gene Order; D006801:Humans; D007438:Introns; D008954:Models, Biological; D059372:Nucleotide Motifs; D011485:Protein Binding; D022821:RNA Splice Sites; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; C571219:L4-22K protein, adenovirus; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D017361:Viral Nonstructural Proteins