nol11, implicated in the pathogenesis of north american indian childhood cirrhosis, is required for pre-rrna transcription and processingnol11,与北美印第安儿童肝硬化的发病机理,需要pre-rrna转录和处理.pdfVIP

NOL11, Implicated in the Pathogenesis of North American Indian Childhood Cirrhosis, Is Required for Pre- rRNA Transcription and Processing 1 ´ 2 1 2 1,3,4 Emily F. Freed , Jose-Luis Prieto , Kathleen L. McCann , Brian McStay , Susan J. Baserga * 1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2 Centre for Chromosome Biology, School of Life Sciences, National University of Ireland Galway, Galway, Ireland, 3 Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America, 4 Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America Abstract The fundamental process of ribosome biogenesis requires hundreds of factors and takes place in the nucleolus. This process has been most thoroughly characterized in baker’s yeast and is generally well conserved from yeast to humans. However, some of the required proteins in yeast are not found in humans, raising the possibility that they have been replaced by functional analogs. Our objective was to identify non-conserved interaction partners for the human ribosome biogenesis factor, hUTP4/Cirhin, since the R565W mutation in the C-terminus of hUTP4/Cirhin was reported to cause North American Indian childhood cirrhosis (NAIC). By screening a yeast two-hybrid cDNA library derived from human liver, and through affinity purification followed by mass spectrometry, we identified an uncharacterized nucleolar protein, NOL11, as an interaction partner for hUTP4/Cirhin. Bioinformatic analysis revealed that NOL11 is conserved throughout metazoans and