Acyl-CoAs from coenzyme ribozymes.
We describe in vitro selection of two novel ribozymes that mediate coenzyme reactions. The first is a trans-capping ribozyme that attaches coenzyme A (CoA) at the 5' end of any RNA with the proper short terminal sequence, including RNAs with randomized internal sequences. From such a trans-capped CoA-RNA pool, we derive ribozymes that attack biotinyl-AMP using the SH group of CoA. These ribozymes, selected to acylate CoA with the valeryl side chain of biotin, also produce the crucial metabolic intermediates acetyl-CoA and butyryl-CoA with substantial velocities. Thus, we argue that RNAs might have used the chemical functionality offered by coenzymes to support an RNA world metabolism. In particular, we can combine our results with those of other labs to argue that simple chemistry and RNA catalysis suffice to proceed from simple chemicals to catalysis with acyl-CoAs. The trans-capping method can be generalized for production of varied coenzyme ribozymes using a single catalytic RNA subunit. Finally, the long-suggested RNA origin for CoA itself appears to be chemically feasible.
Jadhav
Vasant R
VR
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309-03, USA.
Yarus
Michael
M
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D001483:Base Sequence; D019921:Biotinylation; D002384:Catalysis; D015723:Gene Library; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012315:RNA Caps / Q000737:chemistry / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*
D000214:Acyl Coenzyme A; D009838:Oligodeoxyribonucleotides; D012315:RNA Caps; D016337:RNA, Catalytic; C024343:butyryl-coenzyme A; D000249:Adenosine Monophosphate; D000105:Acetyl Coenzyme A