RNA damage in biological conflicts and the diversity of responding RNA repair systems

Abstract

RNA is targeted in biological conflicts by enzymatic toxins or effectors. A vast diversity of systems which repair or ‘heal’ this damage has only recently become apparent. Here, we summarize the known effectors, their modes of action, and RNA targets before surveying the diverse systems which counter this damage from a comparative genomics viewpoint. RNA-repair systems show a modular organization with extensive shuffling and displacement of the constituent domains; however, a general ‘syntax’ is strongly maintained whereby systems typically contain: a RNA ligase (either ATP-grasp or RtcB superfamilies), nucleotidyltransferases, enzymes modifying RNA-termini for ligation (phosphatases and kinases) or protection (methylases), and scaffold or cofactor proteins. We highlight poorly-understood or previously-uncharacterized repair systems and components, e.g. potential scaffolding cofactors (Rot/TROVE and SPFH/Band-7 modules) with their respective cognate non-coding RNAs (YRNAs and a novel tRNA-like molecule) and a novel nucleotidyltransferase associating with diverse ligases. These systems have been extensively disseminated by lateral transfer between distant prokaryotic and microbial eukaryotic lineages consistent with intense inter-organismal conflict. Components have also often been ‘institutionalized’ for non-conflict roles, e.g. in RNA-splicing and in RNAi systems (e.g. in kinetoplastids) which combine a distinct family of RNA-acting prim-pol domains with DICER-like proteins.

Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module and replication enzymes with an ancient connection to “Megavirales”

“…Recently, a comprehensive analysis of viral and cellular primases of the archaeo-eukaryal type (Prim-Pol superfamily), including virus homologs, has been published (Burroughs and Aravind, 2016). The results of the analysis of that second hallmark gene of dsDNA viruses are strikingly similar to our analysis of DNA polymerases detailed here.…”

“…In particular, Prim-Pol proteins of both Herpesvirales and Megavirales resolved as multiple clades, though in that case Alloherpesviridae and Herpesviridae form a clade to the exclusion of Malacoherpesviridae (refer to Fig. 6 in Burroughs and Aravind, 2016, and online material accompanying their paper). All these virus clades are deep in the tree, and, whether coincidentally or not, the closest tree neighbor of Malacoherpesviridae is again Poxviridae, though their joint clade in the Prim-Pol tree is not well-supported.…”

Polyvalent Proteins, a Pervasive Theme in the Intergenomic Biological Conflicts of Bacteriophages and Conjugative Elements

“…The resulting arms race has selected for a wide arsenal of enzymes, both those that damage nucleic acids and those that protect against or help specifically target such damage across diverse conflict and counterconflict systems (9, 10, 65). A second set of enzymatic domains that operates on nucleic acids directly facilitate the replication or transcription of the invasive genome.…”

The unexpected provenance of components in eukaryotic nucleotide-excision-repair and kinetoplast DNA-dynamics from bacterial mobile elements

“…Given that these are likely optimized for the dedicated replication of such small replicons, they in part displaced the ancestral components of the mitochondrial replication system. In parallel, as we had earlier shown [13], central components of the RNA-editing system of the kinetoplast such as the RNA-ligases and end-processing enzymes were also derived from bacteriophage RNA-repair systems. Together with the acquisition of key components DNA replication components, such as the Tc-38 and Topo IA from plasmids, DNA pol I and ATP-dependent ligases from bacteriophages and the primpol from NCLDVs, these probably facilitated the unique structural developments that characterize kDNA.…”

“…Aside from these, a member of the archaeo-eukaryotic primase superfamily PPL1, which functions as both a primase and a polymerase (primpol) has been proposed to be involved in both mitochondrial and nuclear DNA replication [73]. We have earlier demonstrated all eukaryotic primpols were ultimately inherited from a nucleo-cytoplasmic large DNA virus (NCLDV)-like source [13, 74]. Thus, several key kDNA replication components appear to have been acquired from not just plasmids/conjugative elements but also bacteriophages and eukaryotic viruses.…”