ISG20L2, a novel vertebrate nucleolar exoribonuclease involved in ribosome biogenesis.
Proteomics analyses of human nucleoli provided molecular bases for an understanding of the multiple functions fulfilled by these nuclear domains. However, the biological roles of about 100 of the identified proteins are unpredictable. The present study describes the functional characterization of one of these proteins, ISG20L2. We demonstrate that ISG20L2 is a 3' to 5' exoribonuclease involved in ribosome biogenesis at the level of 5.8 S rRNA maturation, more specifically in the processing of the 12 S precursor rRNA. The use of truncated forms of ISG20L2 demonstrated that its N-terminal half promotes the nucleolar localization and suggested that its C-terminal half bears the exoribonuclease activity. Identification of the binding partners of ISG20L2 confirmed its involvement in the biogenesis of the large ribosomal subunit. These results strongly support the notion that, in human, as it was demonstrated in yeast, 5.8 S rRNA maturation requires several proteins in addition to the exosome complex. Furthermore this observation greatly sustains the idea that the extremely conserved need for correctly processed rRNAs in vertebrates and yeast is achieved by close but different mechanisms.
Couté
Yohann
Y
Biomedical Proteomics Research Group, Département de Biologie Structurale et Bioinformatique, Centre Médical Universitaire, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland. yohann.coute@medecine.unige.ch
Kindbeiter
Karine
K
Belin
Stéphane
S
Dieckmann
Régis
R
Duret
Laurent
L
Bezin
Laurent
L
Sanchez
Jean-Charles
JC
Diaz
Jean-Jacques
JJ
D000595:Amino Acid Sequence; D000818:Animals; D002466:Cell Nucleolus / Q000201:enzymology*; D019295:Computational Biology; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012322:RNA Precursors / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013379:Substrate Specificity; D014714:Vertebrates
D050505:Mutant Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C505243:AEN protein, human; D005090:Exodeoxyribonucleases