Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.

TitleTarget Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.
Publication TypeJournal Article
Year of Publication2015
AuthorsLee SR, Pratt GA, Martinez FJ, Yeo GW, Lykke-Andersen J
JournalMol Cell
Volume59
Issue3
Pagination413-25
Date Published2015 Aug 6
ISSN1097-4164
Keywords3' Untranslated Regions, Adenosine Triphosphate, Catalytic Domain, HEK293 Cells, Humans, In Vitro Techniques, Molecular Sequence Data, Mutation, Nonsense Mediated mRNA Decay, RNA, Messenger, Substrate Specificity, Trans-Activators
Abstract

RNA quality-control pathways get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the adenosine triphosphatase (ATPase) cycle of the SF1 helicase Upf1 is required for mRNA discrimination during nonsense-mediated decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD-translation and termination codon-proximal poly(A) binding protein-depend on the ATPase activity of Upf1 to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be a widely used activity in target RNA discrimination.

DOI10.1016/j.molcel.2015.06.036
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/26253027?dopt=Abstract
Alternate JournalMol. Cell
PubMed ID26253027
PubMed Central IDPMC4673969
Grant ListHG004659 / HG / NHGRI NIH HHS / United States
HG007005 / HG / NHGRI NIH HHS / United States
NS075449 / NS / NINDS NIH HHS / United States
R01 GM084317 / GM / NIGMS NIH HHS / United States
R01 GM099717 / GM / NIGMS NIH HHS / United States
R01 GM099717 / GM / NIGMS NIH HHS / United States
R01 HG004659 / HG / NHGRI NIH HHS / United States
R01 NS075449 / NS / NINDS NIH HHS / United States
T32 GM008666 / GM / NIGMS NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology