title: The p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated HuR from mRNP.
abstract: The assembly and disassembly of ribonucleoproteins (RNPs) are dynamic processes that control every step of RNA metabolism, including mRNA stability. However, our knowledge of how RNP remodeling is achieved is largely limited to RNA helicase functions. Here, we report a previously unknown mechanism that implicates the ATPase p97, a protein-remodeling machine, in the dynamic regulation of mRNP disassembly. We found that p97 and its cofactor, UBXD8, destabilize p21, MKP-1, and SIRT1, three established mRNA targets of the RNA-binding protein HuR, by promoting release of HuR from mRNA. Importantly, ubiquitination of HuR with a short K29 chain serves as the signal for release. When cells are subjected to stress conditions, the steady-state levels of HuR ubiquitination change, suggesting a new mechanism through which HuR mediates the stress response. Our studies reveal a new paradigm in RNA biology: nondegradative ubiquitin signaling-dependent disassembly of mRNP promoted by the p97-UBXD8 complex to control mRNA stability.
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA. hlzhou@moon.ibp.ac.cn
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Zhou
authors.forename: Cuiyu
authors.initials: C
authors.lastname: Geng
authors.forename: Guangbin
authors.initials: G
authors.lastname: Luo
authors.forename: Hua
authors.initials: H
authors.lastname: Lou
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D013312:Stress, Physiological; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D001798:Blood Proteins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051959:ELAV Proteins; C468782:FAF2 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D025801:Ubiquitin; C026452:messenger ribonucleoprotein; D000251:Adenosine Triphosphatases; C404942:p97 ATPase
keywords: HuR; mRNA stability; ubiquitin