title: Characterization of the nuclear matrix targeting sequence (NMTS) of the BPV1 E8/E2 protein--the shortest known NMTS.
abstract: Technological advantages in sequencing and proteomics have revealed the remarkable diversity of alternative protein isoforms. Typically, the localization and functions of these isoforms are unknown and cannot be predicted. Also the localization signals leading to particular subnuclear compartments have not been identified and thus, predicting alternative functions due to alternative subnuclear localization is limited only to very few subnuclear compartments. Knowledge of the localization and function of alternative protein isoforms allows for a greater understanding of cellular complexity. In this article, we characterize a short and well-defined signal targeting the bovine papillomavirus type 1 E8/E2 protein to the nuclear matrix. The targeting signal comprises the peptide coded by E8 ORF, which is spliced together with part of the E2 ORF to generate the E8/E2 mRNA. Localization to the nuclear matrix correlates well with the transcription repression activities of E8/E2; a single point mutation directs the E8/E2 protein into the nucleoplasm, and transcription repression activity is lost. Our data prove that adding as few as ˜10 amino acids by alternative transcription/alternative splicing drastically alters the function and subnuclear localization of proteins. To our knowledge, E8 is the shortest known nuclear matrix targeting signal.
authors.affiliation: a Estonian Biocentre ; Tartu , Estonia.
authors.forename: Eve
authors.initials: E
authors.lastname: Sankovski
authors.forename: Kristiina
authors.initials: K
authors.lastname: Karro
authors.forename: Mari
authors.initials: M
authors.lastname: Sepp
authors.forename: Reet
authors.initials: R
authors.lastname: Kurg
authors.forename: Mart
authors.initials: M
authors.lastname: Ustav
authors.forename: Aare
authors.initials: A
authors.lastname: Abroi
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D016466:CHO Cells; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D063185:Epigenetic Repression; D016679:Genome, Viral; D015530:Nuclear Matrix / Q000235:genetics* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; C118416:E8 protein, Bovine papillomavirus; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins
keywords: alternative protein isoform; alternative splicing; alternative transcription; molecular trafficking; nuclear matrix targeting sequence; nuclear organelles; nuclear structures; papillomavirus; subnuclear compartmentalisation