Revisiting the Yeast PPR Proteins—Application of an Iterative Hidden Markov Model Algorithm Reveals New Members of the Rapidly Evolving Family

Abstract

Pentatricopeptide repeat (PPR) proteins are the largest known RNA-binding protein family, and are found in all eukaryotes, being particularly abundant in higher plants. PPR proteins localize mostly to mitochondria and chloroplasts, and many were shown to modulate organellar genome expression on the posttranscriptional level. Although the genomes of land plants encode hundreds of PPR proteins, only a few have been identified in Fungi and Metazoa. As the current PPR motif profiles are built mainly on the basis of the predominant plant sequences, they are unlikely to be optimal for detecting fungal and animal members of the family, and many putative PPR proteins in these genomes may remain undetected. In order to verify this hypothesis, we designed a hidden Markov model-based bioinformatic tool called Supervised Clustering-based Iterative Phylogenetic Hidden Markov Model algorithm for the Evaluation of tandem Repeat motif families (SCIPHER) using sequence data from orthologous clusters from available yeast genomes. This approach allowed us to assign 12 new proteins in Saccharomyces cerevisiae to the PPR family. Similarly, in other yeast species, we obtained a 5-fold increase in the detection of PPR motifs, compared with the previous tools. All the newly identified S. cerevisiae PPR proteins localize in the mitochondrion and are a part of the RNA processing interaction network. Furthermore, the yeast PPR proteins seem to undergo an accelerated divergent evolution. Analysis of single and double amino acid substitutions in the Dmr1 protein of S. cerevisiae suggests that cooperative interactions between motifs and pseudoreversion could be the force driving this rapid evolution.

A Trypanosomal Pentatricopeptide Repeat Protein Stabilizes the Mitochondrial mRNAs of Cytochrome Oxidase Subunits 1 and 2

“…A recent characterization of PPR proteins required for polyadenylation reached the same conclusion (2). Moreover, using more sophisticated bioinformatic protocols, the set of known PPR proteins has also been expanded in other organisms, such as Saccharomyces cerevisiae (19) and Schizosaccharomyces pombe (17). Thus, it is likely that mammals also have a higher number of PPR proteins than is anticipated right now.…”

Pentatricopeptide motifs in the N-terminal extension domain of yeast mitochondrial RNA polymerase Rpo41p are not essential for its function

“…Using yeast-specific profiles and orthologous alignments from different yeast genomes [35], five divergent PPR motifs can be, however, identified in S.…”

“…Arrows indicate the positions of pentatricopeptide (PPR) motifs predicted in silico [35]. Numbers indicate amino acid positions, for the three named PPR motifs that were studied here, the position of the first amino acid is shown.…”

“…In the human mtRNAP this extension is joined to the NTD by a helical domain containing two pentatricopeptide (PPR) motifs [29]. Whereas no significant sequence similarity can be found between the N-terminal extension of human POLRMT and yeast Rpo41p, application of an algorithm fine-tuned for detection of yeast pentatricopeptide proteins indicated that up to five putative PPR motifs can be found in the Nterminal part of Rpo41p [35].…”

The Importance of the 45 S Ribosomal Small Subunit-related Complex for Mitochondrial Translation in Trypanosoma brucei

“…For comparison, 15 PPR proteins have been found in baker's yeast and seven in mammals (32,33). It is plausible that this abundance is related to the higher complexity of the mRNA processing and translation machineries and their increased reliance on sequence-specific RNA recognition, as compared with other organisms.…”