Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

Abstract

5Divalent metal cations are essential to the structure and function of the ribosome. Previous 2 6 characterizations of ribosome structure and function performed under standard laboratory 2 7conditions have implicated Mg 2+ as the primary mediator of ribosomal structure and function. 8The contribution of Fe 2+ as a ribosomal cofactor has been largely overlooked, despite the 2 9 ribosome's evolution in a high Fe 2+ environment, and its continued use by obligate anaerobes 3 0 inhabiting high Fe 2+ niches. Here we show that (i) iron readily cleaves RNA by a non-oxidative 3 1 mechanism that has not been detected previously, (ii) functional ribosomes purified from cells 3 2 grown under low O 2 , high Fe 2+ conditions are associated with Fe 2+ , (iii) a small subset of Fe 2+ 3 3that is associated with the ribosome is not exchangeable with surrounding cations, presumably 3 4 because they are highly coordinated by rRNA. In total, these results expand the ancient role of 3 5 iron in biochemistry, suggest a novel method for regulation of translation by iron, and highlight a 3 6 possible new mechanism of iron toxicity. 3 7

Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules

“…Besides an important impact on new biochemical features of a ribosome and medicine-related translational science, this technically advanced approach provided the scientific community with an elaborate biological model crucial for investigating the origin of life and evolution of biological molecules. In fact, the recapitulated conditions mimicking the anoxic Earth environment supported a hypothesis that a ribosome represents an extraordinarily well-conserved RNA-protein structure that existed in a complex with iron ions when Earth's atmosphere was depleted of oxygen (3,20). These studies were corroborated with biochemical assays conducted with ribosomes from Saccharomyces cerevisiae, wherein it was demonstrated that eukaryotic ribosomes maintained an ability to interact with Fe 2+ at the selected sites under normal physiological conditions.…”

“…The unique chemical properties of numerous metal ions facilitate extensive interactions with biomolecules, with impacts across all areas of cellular activity, including fundamental processes, such as respiration, metabolism, nitrogen fixation, photosynthesis, DNA replication, transcription and protein synthesis (1)(2)(3)(4)(5)(6)(7)(8). At least ten metal elements are considered essential for most forms of life (9), including six of the d-block elements of the periodic table: manganese, iron, cobalt, nickel, copper, and zinc (10) and Figure 1A.…”

The czcD (NiCo) Riboswitch Responds to Iron(II)

“…It is also possible that different czcD riboswitches will play distinct roles depending on the organism. Although Fe II −RNA interactions have been proposed to have been important in the early earth 50 and perhaps even in the extant world, 30 a function of Fe II as the cognate ligand of a riboswitch would represent a new mechanism of iron regulation in the human commensal and pathogenic bacteria that contain it. Further characterization of metal ion−riboswitch interactions, the physiological roles of the riboswitch and the genes regulated by it, the interplay between riboswitch-and transcription factor-mediated regulation of cellular metal ion concentrations, and the role of metal excess in the health-relevant bacteria in which this riboswitch is found is the focus of our further investigations.…”

Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids

“…Though requires phosphorylated monomers and many branching reactions possible given the various nucleophilic moieties on nucleotides [18,35–37]functional (catalytic) capacitydiverse. Could have supported early metabolism [38,39]limited primarily to phosphoryl group transfer chemistry (with the important exception of the ribosome, which catalyses aminolysis of esters) [38]cofactor utilization4diverse [40–42]limited primarily to Mg 2+ [43–46]tolerance to backbone impuritysubstitution of amides for esters associated with incremental decreases in stability [13,47,48]base-pairing possible with diverse backbones (peptides, other sugars [49]), though typically tertiary structures not compatible [50]pH tolerancehigh—stable between 3 and 10low—stable between 5 and 7—due to both backbone cleavage and depurinationtolerance to high Fe 2+ levels (and other divalent cations)high [43,51–53]low—catalyses hydrolysis of phosphodiesters through ‘in-line’ and Fenton mechanisms [45,46]unassisted refoldability5generally, yes. Complex proteins may require chaperones or translation, but simple proteins can fold unassisted [54,55]generally, no.…”