B23 acts as a nucleolar stress sensor and promotes cell survival through its dynamic interaction with hnRNPU and hnRNPA1.
The nucleolus is one of the functional nuclear compartments in which the ribosome biogenesis takes place. Proteomic analysis revealed a large number of nucleolar proteins that are involved in diverse cellular processes, including biogenesis of ribonucleoprotein particles, stress responses, cell proliferation and cell cycle progression. Here, we report that in response to transcription repression-induced nucleolar segregation, B23, a nucleolar protein required for rRNA processing, is localized to the cytoplasm and forms a complex with the mRNA-binding proteins hnRNPU and hnRNPA1 in a sequential manner. In addition, RNA Polymerase I, but not RNA Polymerase II inhibition, was found to account for the translocation-dependent assembly of B23/hnRNPU/hnRNPA1. We also showed that interactions among these proteins are regulated by hnRNPU-bound mRNAs such as the 3'-untranslated region (UTR) of Bcl-xL mRNA. Ectopically expressed 3'-UTR of Bcl-xL mRNA, which disrupted the interactions among B23, hnRNPU and hnRNPA1, led to enhanced cell apoptosis induced by either actinomycin D treatment or mitotic arrest. Overall, these data highlight a novel function of B23 as a stress sensor in the assembly of B23/hnRNPU/hnRNPA1 complex to promote cell survival.
Yao
Z
Z
Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
Duan
S
S
Hou
D
D
Wang
W
W
Wang
G
G
Liu
Y
Y
Wen
L
L
Wu
M
M
D020413:3' Untranslated Regions / Q000235:genetics*; D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology; D002466:Cell Nucleolus / Q000235:genetics* / Q000502:physiology; D002470:Cell Survival / Q000235:genetics; D004256:DNA Polymerase I / Q000235:genetics; D006367:HeLa Cells; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D000090243:Nucleophosmin; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology; D014158:Transcription, Genetic; D051020:bcl-X Protein / Q000235:genetics
D020413:3' Untranslated Regions; C494811:BCL2L1 protein, human; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051020:bcl-X Protein; C000619656:hnRNPA1 protein, human; D000090243:Nucleophosmin; D004256:DNA Polymerase I; D012259:Ribonuclease, Pancreatic