Abstract
Ribosomal biogenesis has been extensively investigated, especially to identify the elusive nucleases and cofactors involved in the complex rRNA processing events in eukaryotes. Large-scale screens in yeast identified two biochemically uncharacterized proteins, TSR3 and TSR4, as being key players required for rRNA maturation. Using multiple computational approaches we identify the conserved domains comprising these proteins and establish sequence and structural features providing novel insights regarding their roles. TSR3 is unified with the DTW domain into a novel superfamily of predicted enzymatic domains, with the balance of the available evidence pointing toward an RNase role with the archaeo-eukaryotic TSR3 proteins processing rRNA and the bacterial versions potentially processing tRNA. TSR4, its other eukaryotic homologs PDCD2/rp-8, PDCD2L, Zfrp8, and trus, the predominantly bacterial DUF1963 proteins, and other uncharacterized proteins are unified into a new domain superfamily, which arose from an ancient duplication event of a strand-swapped, dimer-forming all-beta unit. We identify conserved features mediating protein-protein interactions (PPIs) and propose a potential chaperone-like function. While contextual evidence supports a conserved role in ribosome biogenesis for the eukaryotic TSR4-related proteins, there is no evidence for such a role for the bacterial versions. Whereas TSR3-related proteins can be traced to the last universal common ancestor (LUCA) with a well-supported archaeo-eukaryotic branch, TSR4-related proteins of eukaryotes are derived from within the bacterial radiation of this superfamily, with archaea entirely lacking them. This provides evidence for “systems admixture,” which followed the early endosymbiotic event, playing a key role in the emergence of the uniquely eukaryotic ribosome biogenesis process.
Highlights
Ribosomal RNAs combine with structural proteins in assembly of the ribosome, the ribonucleoprotein protein synthesis complex conserved across the three superkingdoms of cellular life
The polycistronic precursor is processed into the mature 18S Ribosomal RNAs (rRNAs) transcript, which is assembled into the small ribosomal subunit and the mature 5.8S and 25S/28S rRNA transcripts which are assembled into the large ribosomal subunit
The previouslyidentified archaeal and eukaryotic TSR3 homologs (Armengaud et al, 2005) were recovered within the first two iterations. In addition to these known homologs, we recovered a set of bacterial sequences with no previous domain annotation and recovered bacterial and eukaryotic homologs of the DTWD1 and DTWD2 proteins, both of which are annotated in Pfam as containing the functionally uncharacterized DTW domain
Summary
Ribosomal RNAs (rRNAs) combine with structural proteins in assembly of the ribosome, the ribonucleoprotein protein synthesis complex conserved across the three superkingdoms of cellular life. While there are notable differences between bacteria, archaea, and eukaryotes, the general steps in rRNA production are shared. These broadly entail transcription of a polycistronic precursor, which is subject to a complex series of processing events involving the interplay between distinct endo- and exo-nucleases (Deutscher, 2009; Mullineux and Lafontaine, 2012; Yip et al, 2013). The polycistronic precursor is processed into the mature 16S transcript, which is incorporated into the small subunit and the 5S and 23S rRNA transcripts, which are assembled into the large subunit
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