Cryo-EM Structures of Saccharolobus solfataricus Initiation Complexes with Leaderless mRNAs Highlight Archaeal Features and Eukaryotic Proximity

Abstract

The archaeal ribosome is of the eukaryotic type. Genomic and phylogenetic studies have indicated that TACK and Asgard, the closest relatives of eukaryotes, have ribosomes containing eukaryotic ribosomal proteins not found in other archaeal branches, eS25, eS26 and eS30. In our study, we investigated the case of Saccharolobus solfataricus, a crenarchaeon belonging to the TACK branch, which mainly uses leaderless mRNAs. We characterized the small ribosomal subunit of S. solfataricus bound to SD-leadered or leaderless mRNAs (lmRNAs). Cryo-EM structures show for the first time archaeal versions of eS25, eS26 and eS30 proteins bound to the small subunit. In addition, we identify two novel ribosomal proteins named aS33 and aS34 as well as a domain of eS6, that highlight the diversity of archaeal ribosomes. Leaderless mRNAs are bound to the small ribosomal subunit, and the 5-triphosphate group contributes to their binding. Archaeal eS26 is in the mRNA exit channel wrapped around the 3 end of ribosomal RNA, as it is in eukaryotes. Its position is not compatible with an SD:antiSD duplex in the mRNA exit channel. Overall, our results suggest a role of eS26 in translation regulation and possible evolutionary routes from archaeal to eukaryotic translation.