title: Evolutionary conservation of the ribosomal biogenesis factor Rbm19/Mrd1: implications for function.
abstract: Ribosome biogenesis in eukaryotes requires coordinated folding and assembly of a pre-rRNA into sequential pre-rRNA-protein complexes in which chemical modifications and RNA cleavages occur. These processes require many small nucleolar RNAs (snoRNAs) and proteins. Rbm19/Mrd1 is one such protein that is built from multiple RNA-binding domains (RBDs). We find that Rbm19/Mrd1 with five RBDs is present in all branches of the eukaryotic phylogenetic tree, except in animals and Choanoflagellates, that instead have a version with six RBDs and Microsporidia which have a minimal Rbm19/Mrd1 protein with four RBDs. Rbm19/Mrd1 therefore evolved as a multi-RBD protein very early in eukaryotes. The linkers between the RBDs have conserved properties; they are disordered, except for linker 3, and position the RBDs at conserved relative distances from each other. All but one of the RBDs have conserved properties for RNA-binding and each RBD has a specific consensus sequence and a conserved position in the protein, suggesting a functionally important modular design. The patterns of evolutionary conservation provide information for experimental analyses of the function of Rbm19/Mrd1. In vivo mutational analysis confirmed that a highly conserved loop 5-β4-strand in RBD6 is essential for function.
authors.affiliation: Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kallberg
authors.forename: Åsa
authors.initials: Å
authors.lastname: Segerstolpe
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lackmann
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
authors.forename: Lars
authors.initials: L
authors.lastname: Wieslander
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D016681:Genome, Fungal / Q000235:genetics; D006801:Humans; D016816:Microsporida / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D015203:Reproducibility of Results; D012270:Ribosomes / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C530595:Mrd1 protein, S cerevisiae; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins