title: Non-stop mRNA decay initiates at the ribosome.
abstract: The translation machinery deciphers genetic information encoded within mRNAs to synthesize proteins needed for various cellular functions. Defective mRNAs that lack in-frame stop codons trigger non-productive stalling of ribosomes. We investigated how cells deal with such defective mRNAs, and present evidence to demonstrate that RNase R, a processive 3'-to-5' exoribonuclease, is recruited to stalled ribosomes for the specific task of degrading defective mRNAs. The recruitment process is selective for non-stop mRNAs and is dependent on the activities of SmpB protein and tmRNA. Most intriguingly, our analysis reveals that a unique structural feature of RNase R, the C-terminal lysine-rich (K-rich) domain, is required both for productive ribosome engagement and targeted non-stop mRNA decay activities of the enzyme. These findings provide new insights into how a general RNase is recruited to the translation machinery and highlight a novel role for the ribosome as a platform for initiating non-stop mRNA decay.
authors.affiliation: Center for Infectious Diseases, Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Ge
authors.forename: Preeti
authors.initials: P
authors.lastname: Mehta
authors.forename: Jamie
authors.initials: J
authors.lastname: Richards
authors.forename: A Wali
authors.initials: AW
authors.lastname: Karzai
mesh_terms: D018388:Codon, Terminator; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018388:Codon, Terminator; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; D005095:Exoribonucleases; C080868:ribonuclease R