rRNA expansion segment 7 in eukaryotes: from Signature Fold to tentacles

Abstract

The ribosomal core is universally conserved across the tree of life. However, eukaryotic ribosomes contain diverse rRNA expansion segments (ESs) on their surfaces. Sites of ES insertions are predicted from sites of insertion of micro-ESs in archaea. Expansion segment 7 (ES7) is one of the most diverse regions of the ribosome, emanating from a short stem loop and ranging to over 750 nucleotides in mammals. We present secondary and full-atom 3D structures of ES7 from species spanning eukaryotic diversity. Our results are based on experimental 3D structures, the accretion model of ribosomal evolution, phylogenetic relationships, multiple sequence alignments, RNA folding algorithms and 3D modeling by RNAComposer. ES7 contains a distinct motif, the ‘ES7 Signature Fold’, which is generally invariant in 2D topology and 3D structure in all eukaryotic ribosomes. We establish a model in which ES7 developed over evolution through a series of elementary and recursive growth events. The data are sufficient to support an atomic-level accretion path for rRNA growth. The non-monophyletic distribution of some ES7 features across the phylogeny suggests acquisition via convergent processes. And finally, illustrating the power of our approach, we constructed the 2D and 3D structure of the entire LSU rRNA of Mus musculus.

TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

“…Previous studies suggested that expansion segments can serve as interaction platforms for ribosome-associated factors, binding with specific mRNAs, regulating translation fidelity, and controlling compartment-specific translation (145)(146)(147)(148)(149). ES7L, the largest eukaryotic expansion segment, contains a highly conserved core signature fold and long tentacle-like extensions that undergo rapid evolutionary changes (150). In yeast, the rRNA expansion segment ES7L was proposed to bind aminoacyl tRNA synthetases, potentially modulating translation efficiency (146).…”

The Importance of Being RNA-est: considering RNA-mediated ribosome plasticity

“…An evolutionary increase in rRNA size and complexity has most commonly been observed through the insertion of so-called expansion segments (ESs), GC-rich insertions of varying lengths into the rDNA sequence [ 18 ]. Guided by information from both high-resolution 3D and secondary structure modelling, a model has emerged, termed ‘the accretion model’, which implies a general tendency towards molecular growth, i.e., expansion, of rRNA [ 39 ]. According to its principles, rRNA expanded iteratively and incrementally in size during evolution without a substantial remodelling of the ribosome’s core or common trunk; as such, ES sites have increased as organisms became more complex.…”

“…According to its principles, rRNA expanded iteratively and incrementally in size during evolution without a substantial remodelling of the ribosome’s core or common trunk; as such, ES sites have increased as organisms became more complex. While most commonly observed in eukaryotes, ESs have been identified in the 5S rRNA of 36 bacterial strains and Archaea, which possess ESs with most insertions ranging between~5–20 nt in length at sites that coincide with those of eukaryotic ESs [ 18 , 39 ]. An exception to these short Archaeal ESs, are the Asgard ES39 and ES9, which have been discovered in the LSU rRNA Asgard archaeal phyla and, ranging in length from 50 to 200 nt, are closer to eukaryotic ESs, where ES39S varies between 80 nt in protists and 138 nt in S.cerevisiae to 178 nt in Drosophila and 231 nt in humans [ 40 ].…”

“…An exception to these short Archaeal ESs, are the Asgard ES39 and ES9, which have been discovered in the LSU rRNA Asgard archaeal phyla and, ranging in length from 50 to 200 nt, are closer to eukaryotic ESs, where ES39S varies between 80 nt in protists and 138 nt in S.cerevisiae to 178 nt in Drosophila and 231 nt in humans [ 40 ]. In birds and mammals, ESs often containing long stretches of GC-rich sequences, exhibiting high sequence and length variability and can span hundreds of angstroms in length, prompting their description as ‘tentacle-like’ rRNA segments, dynamic and flexible in structure [ 39 ]. This flexibility and the fact that their limited interactions with r-proteins have made it difficult to resolve their structure and gain further insight into their functions [ 5 , 16 , 18 , 39 , 41 , 42 ].…”

“…In birds and mammals, ESs often containing long stretches of GC-rich sequences, exhibiting high sequence and length variability and can span hundreds of angstroms in length, prompting their description as ‘tentacle-like’ rRNA segments, dynamic and flexible in structure [ 39 ]. This flexibility and the fact that their limited interactions with r-proteins have made it difficult to resolve their structure and gain further insight into their functions [ 5 , 16 , 18 , 39 , 41 , 42 ].…”