RNA folding and catalysis mediated by iron (II).
Mg²⁺ shares a distinctive relationship with RNA, playing important and specific roles in the folding and function of essentially all large RNAs. Here we use theory and experiment to evaluate Fe²⁺ in the absence of free oxygen as a replacement for Mg²⁺ in RNA folding and catalysis. We describe both quantum mechanical calculations and experiments that suggest that the roles of Mg²⁺ in RNA folding and function can indeed be served by Fe²⁺. The results of quantum mechanical calculations show that the geometry of coordination of Fe²⁺ by RNA phosphates is similar to that of Mg²⁺. Chemical footprinting experiments suggest that the conformation of the Tetrahymena thermophila Group I intron P4-P6 domain RNA is conserved between complexes with Fe²⁺ or Mg²⁺. The catalytic activities of both the L1 ribozyme ligase, obtained previously by in vitro selection in the presence of Mg²⁺, and the hammerhead ribozyme are enhanced in the presence of Fe²⁺ compared to Mg²⁺. All chemical footprinting and ribozyme assays in the presence of Fe²⁺ were performed under anaerobic conditions. The primary motivation of this work is to understand RNA in plausible early earth conditions. Life originated during the early Archean Eon, characterized by a non-oxidative atmosphere and abundant soluble Fe²⁺. The combined biochemical and paleogeological data are consistent with a role for Fe²⁺ in an RNA World. RNA and Fe²⁺ could, in principle, support an array of RNA structures and catalytic functions more diverse than RNA with Mg²⁺ alone.
School of Biology, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
Shreyas S
SS
Athavale
Anton S
AS
Petrov
Chiaolong
C
Hsiao
Derrick
D
Watkins
Caitlin D
CD
Prickett
J Jared
JJ
Gossett
Lively
L
Lie
Jessica C
JC
Bowman
Eric
E
O'Neill
Chad R
CR
Bernier
Nicholas V
NV
Hud
Roger M
RM
Wartell
Stephen C
SC
Harvey
Loren Dean
LD
Williams
D002384:Catalysis; D007501:Iron / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics; D059370:RNA Folding / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics; D016808:Tetrahymena thermophila / Q000235:genetics
D016337:RNA, Catalytic; C427204:hammerhead ribozyme; D012313:RNA; D007501:Iron; D008274:Magnesium