title: Functional interactions between mRNA turnover and surveillance and the ubiquitin proteasome system.
abstract: The proteasome is a critical regulator of protein levels within the cell and is essential for maintaining homeostasis. A functional proteasome is required for effective mRNA surveillance and turnover. During transcription, the proteasome localizes to sites of DNA breaks, degrading RNA polymerase II and terminating transcription. For fully transcribed and processed messages, cytoplasmic surveillance is initiated with the pioneer round of translation. The proteasome is recruited to messages bearing premature termination codons, which trigger nonsense-mediated decay (NMD), as well as messages lacking a termination codon, which trigger nonstop decay, to degrade the aberrant protein produced from these messages. A number of proteins involved in mRNA translation are regulated in part by proteasome-mediated decay, including the initiation factors eIF4G, eIF4E, and eIF3a, and the poly(A)-binding protein (PABP) interacting protein, Paip2. eIF4E-BP (4E-BP) is differentially regulated by the proteasome: truncated to generate a protein with higher eIF4B binding or completely degraded, depending on its phosphorylation status. Finally, a functional proteasome is required for AU-rich-element (ARE)-mediated decay but the specific role the proteasome plays is unclear. There is data indicating the proteasome can bind to AREs, act as an endonuclease, and degrade ARE-binding proteins. How these events interact with the 5'-to-3' and 3'-to-5' decay pathways is unclear at this time; however, data is provided indicating that proteasomes colocalize with Xrn1 and the exosome RNases Rrp44 and Rrp6 in untreated HeLa cells.
authors.affiliation: Veterans Administration Medical Center Research, White River Junction, VT 05009, USA. seth.brooks@dartmouth.edu
authors.forename: Seth A
authors.initials: SA
authors.lastname: Brooks
mesh_terms: D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology*; D059748:Proteolysis; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex