title: The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA.
abstract: Threonylcarbamoyladenosine (t(6)A) is a universal modification found at position 37 of ANN decoding tRNAs, which imparts a unique structure to the anticodon loop enhancing its binding to ribosomes in vitro. Using a combination of bioinformatic, genetic, structural and biochemical approaches, the universal protein family YrdC/Sua5 (COG0009) was shown to be involved in the biosynthesis of this hypermodified base. Contradictory reports on the essentiality of both the yrdC wild-type gene of Escherichia coli and the SUA5 wild-type gene of Saccharomyces cerevisiae led us to reconstruct null alleles for both genes and prove that yrdC is essential in E. coli, whereas SUA5 is dispensable in yeast but results in severe growth phenotypes. Structural and biochemical analyses revealed that the E. coli YrdC protein binds ATP and preferentially binds RNA(Thr) lacking only the t(6)A modification. This work lays the foundation for elucidating the function of a protein family found in every sequenced genome to date and understanding the role of t(6)A in vivo.
authors.affiliation: Department of Microbiology, University of Florida, Gainesville, FL 32611-0700, USA.
authors.forename: Basma
authors.initials: B
authors.lastname: El Yacoubi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lyons
authors.forename: Yulien
authors.initials: Y
authors.lastname: Cruz
authors.forename: Robert
authors.initials: R
authors.lastname: Reddy
authors.forename: Brian
authors.initials: B
authors.lastname: Nordin
authors.forename: Fabio
authors.initials: F
authors.lastname: Agnelli
authors.forename: James R
authors.initials: JR
authors.lastname: Williamson
authors.forename: Paul
authors.initials: P
authors.lastname: Schimmel
authors.forename: Manal A
authors.initials: MA
authors.lastname: Swairjo
authors.forename: Valérie
authors.initials: V
authors.lastname: de Crécy-Lagard
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020043:Genes, Essential; D023281:Genomics; D008969:Molecular Sequence Data; D012343:RNA, Transfer / Q000737:chemistry* / Q000378:metabolism; D012363:RNA, Transfer, Thr / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012363:RNA, Transfer, Thr; D016601:RNA-Binding Proteins; C541142:SUA5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C426646:YrdC protein, E coli; D000255:Adenosine Triphosphate; D012343:RNA, Transfer; D000241:Adenosine