title: The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE.
abstract: Translational control is widely used to adjust gene expression levels. During the stringent response in bacteria, mRNA is degraded on the ribosome by the ribosome-dependent endonuclease, RelE. The molecular basis for recognition of the ribosome and mRNA by RelE and the mechanism of cleavage are unknown. Here, we present crystal structures of E. coli RelE in isolation (2.5 A) and bound to programmed Thermus thermophilus 70S ribosomes before (3.3 A) and after (3.6 A) cleavage. RelE occupies the A site and causes cleavage of mRNA after the second nucleotide of the codon by reorienting and activating the mRNA for 2'-OH-induced hydrolysis. Stacking of A site codon bases with conserved residues in RelE and 16S rRNA explains the requirement for the ribosome in catalysis and the subtle sequence specificity of the reaction. These structures provide detailed insight into the translational regulation on the bacterial ribosome by mRNA cleavage.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Cajetan
authors.initials: C
authors.lastname: Neubauer
authors.forename: Yong-Gui
authors.initials: YG
authors.lastname: Gao
authors.forename: Kasper R
authors.initials: KR
authors.lastname: Andersen
authors.forename: Christine M
authors.initials: CM
authors.lastname: Dunham
authors.forename: Ann C
authors.initials: AC
authors.lastname: Kelley
authors.forename: Jendrik
authors.initials: J
authors.lastname: Hentschel
authors.forename: Kenn
authors.initials: K
authors.lastname: Gerdes
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
authors.forename: Ditlev E
authors.initials: DE
authors.lastname: Brodersen
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D012333:RNA, Messenger / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D016963:Thermus thermophilus / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; C465566:RelE protein, E coli