Evolutionary conservation of the ribosomal biogenesis factor Rbm19/Mrd1: implications for function

PLoS One. 2012;7(9):e43786. doi: 10.1371/journal.pone.0043786. Epub 2012 Sep 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence*
  • DNA Mutational Analysis
  • Evolution, Molecular*
  • Genome, Fungal / genetics
  • Humans
  • Microsporida / genetics
  • Molecular Sequence Data
  • Phylogeny
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics*
  • Reproducibility of Results
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Mrd1 protein, S cerevisiae
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins

Grants and funding

This work was supported by the Swedish Research Council, Carl Tryggers Stiftelse, and Linköping University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.