Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1.
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.
Mesh Terms:
Caffeine, Cell Cycle Proteins, DNA Replication, Hela Cells, Histones, Humans, Hydroxyurea, Lysine, Protein Binding, Protein-Serine-Threonine Kinases, RNA Stability, RNA, Messenger, RNA, Small Interfering, Trans-Activators
Caffeine, Cell Cycle Proteins, DNA Replication, Hela Cells, Histones, Humans, Hydroxyurea, Lysine, Protein Binding, Protein-Serine-Threonine Kinases, RNA Stability, RNA, Messenger, RNA, Small Interfering, Trans-Activators
Nat. Struct. Mol. Biol.
Date: Sep. 01, 2005
PubMed ID: 16086026
View in: Pubmed Google Scholar
Download Curated Data For This Publication
110842
Switch View:
- Interactions 3