Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3
Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorec...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/23244 |
| _version_ | 1811200217761972224 |
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| author | Ritu Chaudhary Berkley Gryder Wendy S Woods Murugan Subramanian Matthew F Jones Xiao Ling Li Lisa M Jenkins Svetlana A Shabalina Min Mo Mary Dasso Yuan Yang Lalage M Wakefield Yuelin Zhu Susan M Frier Branden S Moriarity Kannanganattu V Prasanth Pablo Perez-Pinera Ashish Lal |
| author_facet | Ritu Chaudhary Berkley Gryder Wendy S Woods Murugan Subramanian Matthew F Jones Xiao Ling Li Lisa M Jenkins Svetlana A Shabalina Min Mo Mary Dasso Yuan Yang Lalage M Wakefield Yuelin Zhu Susan M Frier Branden S Moriarity Kannanganattu V Prasanth Pablo Perez-Pinera Ashish Lal |
| author_sort | Ritu Chaudhary |
| collection | DOAJ |
| description | Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells. |
| first_indexed | 2024-04-12T02:00:59Z |
| format | Article |
| id | doaj.art-0e4efcf121494f7b9aa2a822c1a3169e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:00:59Z |
| publishDate | 2017-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0e4efcf121494f7b9aa2a822c1a3169e2022-12-22T03:52:40ZengeLife Sciences Publications LtdeLife2050-084X2017-06-01610.7554/eLife.23244Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3Ritu Chaudhary0Berkley Gryder1Wendy S Woods2Murugan Subramanian3Matthew F Jones4Xiao Ling Li5Lisa M Jenkins6Svetlana A Shabalina7Min Mo8Mary Dasso9Yuan Yang10Lalage M Wakefield11Yuelin Zhu12Susan M Frier13Branden S Moriarity14Kannanganattu V Prasanth15Pablo Perez-Pinera16Ashish Lal17https://orcid.org/0000-0002-4299-8177Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesOncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United StatesLaboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesMolecular Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesIonis Pharmaceuticals, Carlsbad, United StatesDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Twin Cities, United StatesDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United StatesDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United StatesThousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells.https://elifesciences.org/articles/23244p53lncRNAMatrin 3RP3-326I13.1PINCRDNA damage |
| spellingShingle | Ritu Chaudhary Berkley Gryder Wendy S Woods Murugan Subramanian Matthew F Jones Xiao Ling Li Lisa M Jenkins Svetlana A Shabalina Min Mo Mary Dasso Yuan Yang Lalage M Wakefield Yuelin Zhu Susan M Frier Branden S Moriarity Kannanganattu V Prasanth Pablo Perez-Pinera Ashish Lal Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 eLife p53 lncRNA Matrin 3 RP3-326I13.1 PINCR DNA damage |
| title | Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 |
| title_full | Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 |
| title_fullStr | Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 |
| title_full_unstemmed | Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 |
| title_short | Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 |
| title_sort | prosurvival long noncoding rna pincr regulates a subset of p53 targets in human colorectal cancer cells by binding to matrin 3 |
| topic | p53 lncRNA Matrin 3 RP3-326I13.1 PINCR DNA damage |
| url | https://elifesciences.org/articles/23244 |
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