title: The evolutionarily conserved protein Las1 is required for pre-rRNA processing at both ends of ITS2.
abstract: Ribosome synthesis entails the formation of mature rRNAs from long precursor molecules, following a complex pre-rRNA processing pathway. Why the generation of mature rRNA ends is so complicated is unclear. Nor is it understood how pre-rRNA processing is coordinated at distant sites on pre-rRNA molecules. Here we characterized, in budding yeast and human cells, the evolutionarily conserved protein Las1. We found that, in both species, Las1 is required to process ITS2, which separates the 5.8S and 25S/28S rRNAs. In yeast, Las1 is required for pre-rRNA processing at both ends of ITS2. It is required for Rrp6-dependent formation of the 5.8S rRNA 3' end and for Rat1-dependent formation of the 25S rRNA 5' end. We further show that the Rat1-Rai1 5'-3' exoribonuclease (exoRNase) complex functionally connects processing at both ends of the 5.8S rRNA. We suggest that pre-rRNA processing is coordinated at both ends of 5.8S rRNA and both ends of ITS2, which are brought together by pre-rRNA folding, by an RNA processing complex. Consistently, we note the conspicuous presence of ~7- or 8-nucleotide extensions on both ends of 5.8S rRNA precursors and at the 5' end of pre-25S RNAs suggestive of a protected spacer fragment of similar length.
authors.affiliation: Fonds de la Recherche Scientifique, Université Libre de Bruxelles, Charleroi-Gosselies, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Schillewaert
authors.forename: Ludivine
authors.initials: L
authors.lastname: Wacheul
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lhomme
authors.forename: Denis L J
authors.initials: DL
authors.lastname: Lafontaine
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002453:Cell Cycle; D021903:DNA, Ribosomal Spacer; D005095:Exoribonucleases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D054658:Ribosome Subunits, Large / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D004718:Saccharomycetales / Q000378:metabolism*
chemical_list: D021903:DNA, Ribosomal Spacer; C098171:LAS1 protein, S cerevisiae; C552426:Las1L protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; C065039:RNA, ribosomal, 25S; D005095:Exoribonucleases
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