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

Divalent metal cations are essential to the structure and function of the ribosome. Previous characterizations of the ribosome performed under standard laboratory conditions have implicated Mg(2+) as a primary mediator of ribosomal structure and function. Possible contributions of Fe(2+) as a ribosomal cofactor have been largely overlooked, despite the ribosome's early evolution in a high Fe(2+) environment, and the continued use of Fe(2+) by obligate anaerobes inhabiting high Fe(2+) niches. Here, we show that (i) Fe(2+) cleaves RNA by in-line cleavage, a non-oxidative mechanism that has not previously been shown experimentally for this metal, (ii) the first-order in-line rate constant with respect to divalent cations is >200 times greater with Fe(2+) than with Mg(2+), (iii) functional ribosomes are associated with Fe(2+) after purification from cells grown under low O(2) and high Fe(2+) and (iv) a small fraction of Fe(2+) that is associated with the ribosome is not exchangeable with surrounding divalent cations, presumably because those ions are tightly coordinated by rRNA and deeply buried in the ribosome. In total, these results expand the ancient role of iron in biochemistry and highlight a possible new mechanism of iron toxicity.