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. 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. Nuclei of eukaryotic cells are highly organized organelles in which more than 30 different kinds of transient structures, called nuclear domains or nuclear bodies, support the nuclear functions (1Dundr M. Misteli T. Functional architecture in the cell nucleus.Biochem. J. 2001; 356: 297-310Crossref PubMed Scopus (330) Google Scholar). Since the 1960s, it has been known that nucleoli, the most prominent of the nuclear domains, are the sites of ribosome biogenesis. This function gives rise to their characteristic ultrastructural organization in three main compartments, the fibrillar center and the dense fibrillar and granular components (2Melese T. Xue Z. The nucleolus: an organelle formed by the act of building a ribosome.Curr. Opin. Cell Biol. 1995; 7: 319-324Crossref PubMed Scopus (240) Google Scholar). Ribosome biogenesis is a very complex process that involves the synthesis of ribosomal RNAs (rRNAs) 1The abbreviations used are: rRNA, ribosomal RNA; pre-rRNA, precursor rRNA; ISG20L2, interferon-stimulated 20-kDa exonuclease-like 2; DAPI, 4′,6-diamidino-2-phenylindole; co-IP, co-immunoprecipitation; siRNA, small interfering RNA; aa, amino acids; EGFP, enhanced green fluorescent protein; mRNA, messenger RNA; hnRNP, heterogeneous nuclear ribonucleoprotein; PARN, poly(A)-specific ribonuclease. coupled with their extensive processing, the assembly of these rRNAs with ribosomal proteins, and the export of the resulting preribosomal subunits from nuclei to cytoplasm where the final maturation occurs (3Rouquette J. Choesmel V. Gleizes P.E. Nuclear export and cytoplasmic processing of precursors to the 40S ribosomal subunits in mammalian cells.EMBO J. 2005; 24: 2862-2872Crossref PubMed Scopus (139) Google Scholar). rRNA processing mainly consists of base modifications and cleavages (4Olson M.O. Dundr M. Szebeni A. The nucleolus: an old factory with unexpected capabilities.Trends Cell Biol. 2000; 10: 189-196Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar). Precursor rRNAs (pre-rRNAs) contain external and internal sequences that are not present within mature rRNAs. Removal of these sequences is achieved through sequential endonucleolytic and exonucleolytic cleavages, producing mature 18 S, 5.8 S, and 28 S rRNAs. Studies in yeast have identified several factors responsible for such cleavages: the ribonucleoprotein complex RNase MRP and Ngl2p catalyzing endoribonucleolytic processing, Xrn1p and Rat1p that are 5′ to 3′ exonucleases, Rex1p and Rex2p that are 3′ to 5′ exonucleases, and a protein complex named exosome composed of 3′ to 5′ exoribonucleases and putative RNA-binding proteins (5Schmitt M.E. Clayton D.A. Nuclear RNase MRP is required for correct processing of pre-5.8S rRNA in Saccharomyces cerevisiae.Mol. Cell. Biol. 1993; 13: 7935-7941Crossref PubMed Scopus (230) Google Scholar, 6Faber A.W. Van Dijk M. Raue H.A. Ngl2p is a for the final in processing of rRNA in Saccharomyces PubMed Scopus Google Scholar, The 5′ of yeast rRNA is by from an J. 13: PubMed Scopus Google Scholar, A. conserved of the RNase have and functions in the processing of RNase MRP and RNase RNAs in J. 2000; PubMed Scopus Google Scholar, The 3′ of yeast rRNA is by an processing 10: PubMed Scopus Google Scholar). However, the of the factors required for the processing of mature is rRNA maturation that and mature rRNAs is it is highly that eukaryotic as it has been demonstrated for J. The of ribosome in 2000; PubMed Scopus Google Scholar, M. Full Text Full Text PDF PubMed Scopus Google Scholar). yeast, rRNAs to of of ribosome and function by rRNA base PubMed Scopus Google Scholar). in processing are to the of results the in that rRNA processing a in and in in ribosomal PubMed Scopus Google Scholar). Gleizes and V. J. J. A. T. Gleizes P.E. ribosome biogenesis in PubMed Scopus Google that ribosome biogenesis and processing in from from in the biogenesis of ribosome components a in in an old of PubMed Scopus Google Scholar, A. ribosomal protein are in Biol. PubMed Scopus Google Scholar). Ribosome biogenesis requires the of more than factors that are not of the ribosome J. factors involved in ribosome biogenesis in Saccharomyces cerevisiae.Mol. Cell. Biol. PubMed Scopus Google Scholar, J. Ribosome synthesis in Saccharomyces PubMed Scopus Google Scholar). yeast, functional and analyses these factors functional that and from the preribosomal subunits their maturation A. Opin. Cell Biol. PubMed Scopus Google Scholar, the from the to the Cell Biol. 13: Full Text Full Text PDF PubMed Scopus Google Scholar, M. Ribosome assembly in PubMed Scopus Google Scholar). most of the to A. the human nucleolar PubMed Scopus Google Scholar). Furthermore several factors ribosome biogenesis in have to of such proteins is of to the molecular ribosome biogenesis in and their functions in several analyses of human nucleoli to the of more than different proteins M. of the human Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A. A. A. Functional of human Biol. Cell. 13: PubMed Scopus Google Scholar, M. 2005; PubMed Scopus Google Scholar, M. of the nucleolar PubMed Scopus Google Scholar). and analyses the of the identified proteins functional a in ribosome biogenesis was for about of these proteins A. the human nucleolar PubMed Scopus Google Scholar). However, from these it that biological function to more than 100 The present describes the characterization of one of these proteins, named interferon-stimulated 20-kDa exonuclease-like We that ISG20L2 is a of a composed of proteins, of yeast ISG20L2 within nucleoli of cells and an RNAs from their to their ISG20L2 is composed of at functional domains, one at its N-terminal half localization and with the binding partners and the at its C-terminal half the 3′ to 5′ exoribonuclease activity. of ISG20L2 a of the level of the 12 S pre-rRNA, of ISG20L2 an of this The of the proteins with ISG20L2 confirmed that this protein is involved in ribosome biogenesis and most in the biogenesis of the large ribosomal subunit. ISG20L2 is a human involved in ribosome in the of the internal of of the yeast protein in and in We a than or to the of the yeast with multiple with and PubMed Scopus Google Scholar). The was from protein by We used and to large by Biol. 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J. Raue H.A. in the of processing at a in of yeast that PubMed Scopus Google Scholar, A.W. Raue H.A. The and with factors involved in processing of in Saccharomyces 10: PubMed Scopus Google for a human involved in A. of a nuclear Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, a RNase for an Biol. 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Cell. 13: PubMed Scopus Google Scholar, M. 2005; PubMed Scopus Google Scholar, M. of the nucleolar PubMed Scopus Google Scholar). this observation and ISG20L2 was the of ISG20L2 was by of a protein in that was within the nuclear domains as a nucleolar and not to in cell to The mainly in the and the and is with nuclear Cell. PubMed Scopus Google Scholar). 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A. A. Functional of human Biol. Cell. 13: PubMed Scopus Google Scholar, M. 2005; PubMed Scopus Google Scholar, M. of the nucleolar PubMed Scopus Google Scholar). The present that ISG20L2 is a 3′ to 5′ exoribonuclease within to an not localization of the localization of the proteins as as that ISG20L2 within nucleoli of Furthermore a truncated of ISG20L2 its C-terminal half was to within nucleoli as the These results that the N-terminal half of ISG20L2 promotes the nucleolar localization of the that, in its C-terminal ISG20L2 an conserved in the of the of This several such as RNase proteins, the poly(A)-specific and the as as such as that a by the involvement of and 2001; PubMed Scopus Google Scholar, for A. 1993; PubMed Scopus Google Scholar). The of the are involved in biological RNase is involved in the of and 3′ maturation of S and S and small RNAs in RNase is responsible for the of in A. PubMed Scopus Google Scholar, Z. for a process in Full Text Full Text PDF PubMed Scopus Google Scholar, Z. The processing RNase is for maturation of A. 1995; PubMed Scopus Google Scholar, Z. of ribosomal requires the exoribonuclease RNase PubMed Scopus Google Scholar, Z. 3′ is a of the maturation of RNAs in A. PubMed Scopus Google is for small and is involved in the of and Biol. Full Text PDF PubMed Google Scholar, is an of the A. PubMed Scopus Google the proteins and in the processing of MRP RNase and small nuclear RNAs A. conserved of the RNase have and functions in the processing of RNase MRP and RNase RNAs in J. 2000; PubMed Scopus Google and and are involved in by J. A. A. of a cell 3′ for of mammalian Biol. Full Text PDF PubMed Google Scholar, M. The yeast protein is required for Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). these to the of exonucleases, in their of and as RNase and to of and Biol. Full Text PDF PubMed Google Scholar, J. J. A. of the poly(A)-specific is an and poly(A)-specific 3′ Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, of of RNase T. Identification of required for and Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, T. Identification of a human cytoplasmic complex by Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). that ISG20L2 is an exoribonuclease that RNAs from their to their of RNAs by ISG20L2 is characteristic of a of its with a that from its Furthermore that ISG20L2 a for a at the of its to its exoribonuclease as it was for RNase and J. A. A. of a cell 3′ for of mammalian Biol. Full Text PDF PubMed Google Scholar, exoribonuclease involved in of A. PubMed Scopus Google Scholar). that ISG20L2 is a of the in the of The is composed of three in vertebrates and of the in the of These proteins contain a very of the was as a 3′ to 5′ with a for in nucleoli but in The mainly in the and the and is with nuclear Cell. PubMed Scopus Google Scholar, The human and and in 2001; PubMed Scopus Google Scholar). within nucleoli it was identified in analyses of nucleoli from human cells M. of the human Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A. A. A. Functional of human Biol. Cell. 13: PubMed Scopus Google Scholar, M. 2005; PubMed Scopus Google Scholar, M. of the nucleolar PubMed Scopus Google Scholar). protein within nucleoli of cells not ISG20L2, and are of the that within the biological of of the in this nuclear to the biological of ISG20L2, of its binding partners was different proteins with which it identified and it was for nucleolar proteins, the of ISG20L2 with of its partners to the of the ISG20L2 or proteins, to M. A. T. and characterization of the proteins of the ribonucleoprotein 2001; PubMed Scopus Google Scholar, T. M. T. T. of human ribonucleoprotein and the nucleolar protein responsible for Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. T. T. T. T. forms a with protein and and that is of its with preribosomal ribonucleoprotein Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). the identified partners of ISG20L2 have been identified as within nucleoli of cells A. the human nucleolar PubMed Scopus Google Scholar). of are factors involved in ribosome and nucleolar the of in ribosome biogenesis is not it is in multiple this and functions of Cell PubMed Google Scholar). is a nucleolar protein that act as an assembly of ribosomal subunits Szebeni A. M.O. the functional domains of nucleolar protein Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). is involved in 18 S and 28 S rRNA in of mammalian ribosomal Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). of the proteins identified as partners of ISG20L2 are ribosomal proteins, and of are of the large ribosomal subunit. These and the that ISG20L2 within nucleoli of cells strongly that ISG20L2 involved in ribosome biogenesis and most in the processing and assembly of the large ribosomal subunit. The that ISG20L2 and its N-terminal half with the binding mainly proteins involved in ribosome biogenesis and ribosomal 30 different proteins identified as with the N-terminal half of ISG20L2. of are involved in ribosome nucleolar and is involved in synthesis of in of human ribosomal A. PubMed Scopus Google Scholar). The biological roles of and are However, to the yeast proteins and involved in the biogenesis of the large ribosomal J. of the yeast protein in the of 10: PubMed Scopus Google Scholar, putative involved in Saccharomyces ribosome A. PubMed Scopus Google Scholar). of the proteins identified as with are ribosomal proteins, and of to the large ribosomal subunit. These support the notion that ISG20L2 is involved in the biogenesis of the large ribosomal subunit. it that ISG20L2 is composed of main functional domains, one in the N-terminal half of the protein its localization the with its partners and the in the C-terminal half of the protein the of ISG20L2. ribosomal proteins and proteins involved in ribosome unexpected proteins identified as partners of are involved in of these proteins, and are factors involved in and export or of proteins and the Cell Biol. PubMed Scopus Google Scholar). is involved in M. proteins are of Full Text Full Text PDF PubMed Scopus Google Scholar). This that ISG20L2 involved in several biological as it has been demonstrated for of the of the of is that ISG20L2, from an involvement in ribosome an in Identification of the binding partners of ISG20L2 strongly suggested that this protein is involved in the biogenesis of the large ribosomal subunit. a for ISG20L2 in ribosome biogenesis is by the that it nucleoli M. 2005; PubMed Scopus Google Scholar). We that ISG20L2 in the processing of internal its a in the of the 12 S pre-rRNA, its an in the of this identified precursor of the 5.8 S rRNA. yeast, the maturation from the of the 12 S rRNA precursor S to the 5.8 S rRNA is through sequential achieved by different the exosome is to the 5.8 S 30 precursor from the 12 S This precursor is to the S S by and to the 5.8 S precursor by Rex1p the are by the mature 5.8 S rRNA A.W. Van Dijk M. Raue H.A. Ngl2p is a for the final in processing of rRNA in Saccharomyces PubMed Scopus Google Scholar). the maturation of the 5.8 S rRNA is not a human exosome complex has been The a molecular for in and J. Cell Biol. PubMed Scopus Google Scholar). This complex proteins to in the yeast complex. However, its is by the of the which in yeast, that the and of the exosome have and the maturation of the 5.8 S rRNA and of the eukaryotic Full Text Full Text PDF PubMed Scopus Google Scholar, A. is responsible for yeast exosome Biol. PubMed Scopus Google Scholar). was suggested that, as is the in yeast, the exosome is required but not for a maturation of the human 5.8 S rRNA is an RNA-binding protein involved in rRNA 2005; PubMed Scopus Google Scholar). ISG20L2 is one of the factors involved in the processing of the 12 S The that of ISG20L2 a in of the 12 S and the of a the 5.8 S rRNA that to the yeast S rRNA strongly support this However, the molecular by which this occurs to extensive characterization of an that the 5.8 S rRNA of ISG20L2 to the processing of the 12 S rRNA is of that of its yeast the exosome not ISG20L2 and of the binding partners of ISG20L2 identified in this study are of the ISG20L2 is not of the exosome ISG20L2 as a protein involved in the maturation of the 5.8 S rRNA in a to the ISG20L2 through its exoribonuclease or the 12 S or the of the ISG20L2 a of the the in of the 12 S ISG20L2 was and its in ISG20L2 was ISG20L2 is to this that the required for 5.8 S maturation is more complex in than in yeast and requires several proteins in addition to the exosome complex as it has been with the characterization of a human of the exosome is an RNA-binding protein involved in rRNA 2005; PubMed Scopus Google Scholar). an and not in the of of ISG20L2. is in yeast the processing of the S is J. Ribosome synthesis in Saccharomyces PubMed Scopus Google Scholar, A. Gleizes P.E. A. J. A. M. protein with ribosomal Cell. Biol. PubMed Scopus Google Scholar, T. is a nucleolar ribosomal biogenesis J. 2005; PubMed Scopus Google Scholar). The by which this occurs is not but these strongly support the notion that in in yeast, is of the processing the ribosome biogenesis is J. M. an putative is required for a in the assembly of ribosomal subunits in Saccharomyces PubMed Scopus Google Scholar). more and more that rRNAs are for a of the cell of ribosome and function by rRNA base PubMed Scopus Google Scholar). results that proteins involved in the processing and in the of rRNAs to identified and Furthermore these results that the extremely conserved need for rRNAs in vertebrates and yeast is achieved by close but the to of that are to eukaryotic We are to A.