title: Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC-p53 protein interactions.
abstract: The protein p53 plays a crucial role in the regulation of cellular responses to diverse stresses. Thus, a major priority in cell biology is to define the mechanisms that regulate p53 activity in response to stresses or maintain it at basal levels under normal conditions. Moreover, further investigation is required to establish whether RNA participates in regulating p53's interaction with other proteins. Here, by conducting systematic experiments, we discovered a p53 interactor-hnRNPC-that directly binds to p53, destabilizes it, and prevents its activation under normal conditions. Upon doxorubicin treatment, the lncRNA SNHG1 is retained in the nucleus through its binding with nucleolin and it competes with p53 for hnRNPC binding, which upregulates p53 levels and promotes p53-dependent apoptosis by impairing hnRNPC regulation of p53 activity. Our results indicate that a balance between lncRNA SNHG1 and hnRNPC regulates p53 activity and p53-dependent apoptosis upon doxorubicin treatment, and further indicate that a change in lncRNA subcellular localization under specific circumstances is biologically significant.
authors.affiliation: Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.|Key Laboratory for Molecular Enzymology and Engineering (The Ministry of Education), College of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.|Institute of Geriatrics, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Fan
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering (The Ministry of Education), College of Life Sciences, Jilin University, Changchun, Jilin, China yhjin@jlu.edu.cn xfzheng100@126.com fuhj75@126.com.
authors.forename: Yinghua
authors.identifier: 0000-0002-7385-9903
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Baolei
authors.initials: B
authors.lastname: Tian
authors.affiliation: Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China yhjin@jlu.edu.cn xfzheng100@126.com fuhj75@126.com.
authors.forename: Xiaofei
authors.identifier: 0000-0001-6032-729X
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China yhjin@jlu.edu.cn xfzheng100@126.com fuhj75@126.com.
authors.forename: Hanjiang
authors.identifier: 0000-0002-4352-1178
authors.initials: H
authors.lastname: Fu
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D059372:Nucleotide Motifs; D011485:Protein Binding; D055550:Protein Stability; D034443:RNA Transport / Q000187:drug effects*; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C503635:HNRNPC protein, human; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; C000613724:long non-coding RNA SNHG1, human; D004317:Doxorubicin
keywords: SNHG1; doxorubicin; hnRNPC; lncRNA; p53