title: Identification and characterization of a novel ubiquitous nucleolar protein 'NARR' encoded by a gene overlapping the rab34 oncogene.
abstract: There are only few reports on protein products originating from overlapping mammalian genes even though computational predictions suggest that an appreciable fraction of mammalian genes could potentially overlap. Mass spectrometry-based proteomics has now acquired the tools to probe proteins in an unbiased manner, providing direct evidence of the output of the genomic and gene expression machinery. In particular, proteomics can refine gene predictions and discover novel gene-processing events and gene arrangements. Here, we report the mass spectrometric discovery and biochemical validation of the novel protein encoded by a gene overlapping rab34 oncogene. The novel protein is highly conserved in mammals. In humans, it contains 13 distinct Nine-Amino acid Residue-Repeats (NARR) with the consensus sequence PRVIV(S/T)PR in which the serine or threonine residues are phosphorylated during M-phase. NARR is ubiquitously expressed and resides in nucleoli where it colocalizes with ribosomal DNA (rDNA) gene clusters. Its distribution only partially overlaps with upstream binding factor, one of the main regulators of RNA Polymerase I activity, and is entirely uncoupled from it in mitotic cells and upon inhibition of transcription. NARR only partially colocalizes with fibrillarin, the pre-ribosomal RNA-processing protein, positioning NARR in a separate niche within the rDNA cluster.
authors.affiliation: Max Planck Institute for Biochemistry, Department of Proteomics and Signal Trasduction, Am Klopferspitz 18, Martinsried D 82152, Germany.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zougman
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wisniewski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000737:chemistry*; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D020459:Genes, rRNA; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes; D010448:Peptide Initiation Factors / Q000378:metabolism; D010454:Peptide Termination Factors / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins / Q000032:analysis; D016601:RNA-Binding Proteins / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D020691:rab GTP-Binding Proteins / Q000235:genetics; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D010448:Peptide Initiation Factors; D010454:Peptide Termination Factors; D035463:Pol1 Transcription Initiation Complex Proteins; D016601:RNA-Binding Proteins; D020691:rab GTP-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C489002:ETF1 protein, human; C567953:RAB34 protein, human; C047458:fibrillarin; C063844:transcription factor UBF