The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE

TY - JOUR

T1 - The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE

AU - Neubauer, Cajetan

AU - Gao, Yong-Gui

AU - Andersen, Kasper Røjkjær

AU - Dunham, Christine M

AU - Kelley, Ann C

AU - Hentschel, Jendrik

AU - Gerdes, Kenn

AU - Ramakrishnan, V

AU - Brodersen, Ditlev E

PY - 2009/12/11

Y1 - 2009/12/11

N2 - 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.

AB - 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.

KW - Bacterial Toxins

KW - Escherichia coli

KW - Escherichia coli Proteins

KW - Models, Molecular

KW - RNA, Messenger

KW - RNA, Ribosomal, 16S

KW - Ribosomes

KW - Thermus thermophilus

U2 - 10.1016/j.cell.2009.11.015

DO - 10.1016/j.cell.2009.11.015

M3 - Journal article

C2 - 20005802

SN - 0092-8674

VL - 139

SP - 1084

EP - 1095

JO - Cell

JF - Cell

IS - 6

ER -