Biosynthesis of 7-Deazaguanosine-Modified tRNA Nucleosides: a New Role for GTP Cyclohydrolase I

Author:

Phillips Gabriella1,El Yacoubi Basma1,Lyons Benjamin1,Alvarez Sophie2,Iwata-Reuyl Dirk3,de Crécy-Lagard Valérie1

Affiliation:

1. Department of Microbiology and Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611

2. Donald Danforth Plant Science Center, St. Louis, Missouri 63132

3. Department of Chemistry, Portland State University, Portland, Oregon 97207

Abstract

ABSTRACT Queuosine (Q) and archaeosine (G + ) are hypermodified ribonucleosides found in tRNA. Q is present in the anticodon region of tRNA GUN in Eukarya and Bacteria , while G + is found at position 15 in the D-loop of archaeal tRNA. Prokaryotes produce these 7-deazaguanosine derivatives de novo from GTP through the 7-cyano-7-deazaguanine (pre-Q 0 ) intermediate, but mammals import the free base, queuine, obtained from the diet or the intestinal flora. By combining the results of comparative genomic analysis with those of genetic studies, we show that the first enzyme of the folate pathway, GTP cyclohydrolase I (GCYH-I), encoded in Escherichia coli by folE , is also the first enzyme of pre-Q 0 biosynthesis in both prokaryotic kingdoms. Indeed, tRNA extracted from an E. coli Δ folE strain is devoid of Q and the deficiency is complemented by expressing GCYH-I-encoding genes from different bacterial or archaeal origins. In a similar fashion, tRNA extracted from a Haloferax volcanii strain carrying a deletion of the GCYH-I-encoding gene contains only traces of G + . These results link the production of a tRNA-modified base to primary metabolism and further clarify the biosynthetic pathway for these complex modified nucleosides.

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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