title: Control of mRNA decapping by positive and negative regulatory elements in the Dcp2 C-terminal domain.
abstract: Decapping commits an mRNA to complete degradation and promotes general 5' to 3' decay, nonsense-mediated decay (NMD), and transcript-specific degradation. In Saccharomyces cerevisiae, a single decapping enzyme composed of a regulatory subunit (Dcp1) and a catalytic subunit (Dcp2) targets thousands of distinct substrate mRNAs. However, the mechanisms controlling this enzyme's in vivo activity and substrate specificity remain elusive. Here, using a genetic approach, we show that the large C-terminal domain of Dcp2 includes a set of conserved negative and positive regulatory elements. A single negative element inhibits enzymatic activity and controls the downstream functions of several positive elements. The positive elements recruit the specific decapping activators Edc3, Pat1, and Upf1 to form distinct decapping complexes and control the enzyme's substrate specificity and final activation. Our results reveal unforeseen regulatory mechanisms that control decapping enzyme activity and function in vivo, and define roles for several decapping activators in the regulation of mRNA decapping.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Jacobson
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D004722:Endoribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D012315:RNA Caps / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C488957:EDC3 protein, S cerevisiae; C103266:PAT1 protein, S cerevisiae; D012315:RNA Caps; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C400572:DCP2 protein, S cerevisiae; D004722:Endoribonucleases; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases
keywords: decapping activators; decapping enzyme; mRNA decapping; positive and negative regulation