mRNA 3′ Tagging Is Induced by Nonsense-Mediated Decay and Promotes Ribosome Dissociation

• DOI: 10.1128/mcb.00316-12
• Publication Date: 2012-05-01T04:59:03Z
• Authors: Igor Y. Morozov; Meriel G. Jones; Peter D. Gould; Victoria Crome; James B. Wilson; Anthony J. W. Hall; Daniel J. Rigden; Mark X. Caddick
• Keywords: 0301 basic medicine; Base Sequence; Genes, Fungal; Arabidopsis; RNA, Fungal; Models, Biological; Aspergillus nidulans; Nonsense Mediated mRNA Decay; 03 medical and health sciences; RNA, Plant; Mutation; Humans; RNA 3' End Processing; Ribosomes

For a range of eukaryote transcripts, the initiation of degradation is coincident with the addition of a short pyrimidine tag at the 3' end. Previously, cytoplasmic mRNA tagging has been observed for human and fungal transcripts. We now report that Arabidopsis thaliana mRNA is subject to 3' tagging with U and C nucleotides, as in Aspergillus nidulans. Mutations that disrupt tagging, including A. nidulans cutA and a newly characterized gene, cutB, retard transcript degradation. Importantly, nonsense-mediated decay (NMD), a major checkpoint for transcript fidelity, elicits 3' tagging of transcripts containing a premature termination codon (PTC). Although PTC-induced transcript degradation does not require 3' tagging, subsequent dissociation of mRNA from ribosomes is retarded in tagging mutants. Additionally, tagging of wild-type and NMD-inducing transcripts is greatly reduced in strains lacking Upf1, a conserved NMD factor also required for human histone mRNA tagging. We argue that PTC-induced translational termination differs fundamentally from normal termination in polyadenylated transcripts, as it leads to transcript degradation and prevents rather than facilitates further translation. Furthermore, transcript deadenylation and the consequent dissociation of poly(A) binding protein will result in PTC-like termination events which recruit Upf1, resulting in mRNA 3' tagging, ribosome clearance, and transcript degradation.