title: Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1.
abstract: Eukaryotic cells coordinately regulate histone and DNA synthesis. In mammalian cells, most of the regulation of histone synthesis occurs post-transcriptionally by regulating the concentrations of histone mRNA. As cells enter S phase, histone mRNA levels increase, and at the end of S phase they are rapidly degraded. Moreover, inhibition of DNA synthesis causes rapid degradation of histone mRNAs. Replication-dependent histone mRNAs are the only metazoan mRNAs that are not polyadenylated. Instead, they end with a conserved stem-loop structure, which is the only cis-acting element required for coupling regulation of histone mRNA half-life with DNA synthesis. Here we show that regulated degradation of histone mRNAs requires Upf1, a key regulator of the nonsense-mediated decay pathway, and ATR, a key regulator of the DNA damage checkpoint pathway activated during replication stress.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Handan
authors.initials: H
authors.lastname: Kaygun
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D002110:Caffeine / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D002110:Caffeine; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; C101828:UPF1 protein, human; D008239:Lysine; D006918:Hydroxyurea