title: Serine 192 in the tiny RS repeat of the adenoviral L4-33K splicing enhancer protein is essential for function and reorganization of the protein to the periphery of viral replication centers.
abstract: The adenovirus L4-33K protein is a key regulator involved in the temporal shift from early to late pattern of mRNA expression from the adenovirus major late transcription unit. L4-33K is a virus-encoded alternative splicing factor, which enhances processing of 3' splice sites with a weak sequence context. Here we show that L4-33K expressed from a plasmid is localized at the nuclear margin of uninfected cells. During an infection L4-33K is relocalized to the periphery of E2A-72K containing viral replication centers. We also show that serine 192 in the tiny RS repeat of the conserved carboxy-terminus of L4-33K, which is critical for the splicing enhancer function of L4-33K, is necessary for the nuclear localization and redistribution of the protein to viral replication sites. Collectively, our results show a good correlation between the activity of L4-33K as a splicing enhancer protein and its localization to the periphery of viral replication centers.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 75123 Uppsala, Sweden. sara.ostberg@imbim.uu.se
authors.forename: Sara
authors.initials: S
authors.lastname: Östberg
authors.forename: Heidi
authors.initials: H
authors.lastname: Törmänen Persson
authors.forename: Göran
authors.initials: G
authors.lastname: Akusjärvi
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012694:Serine / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C571219:L4-22K protein, adenovirus; D050505:Mutant Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D012694:Serine