Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3

• Published in: eLife Vol. 6
• Main Authors: Chaudhary, Ritu, Gryder, Berkley, Woods, Wendy S, Subramanian, Murugan, Jones, Matthew F, Li, Xiao Ling, Jenkins, Lisa M, Shabalina, Svetlana A, Mo, Min, Dasso, Mary, Yang, Yuan, Wakefield, Lalage M, Zhu, Yuelin, Frier, Susan M, Moriarity, Branden S, Prasanth, Kannanganattu V, Perez-Pinera, Pablo, Lal, Ashish
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 05.06.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Apoptosis; Binding sites (Biochemistry); Biology; BTG2 protein; Cancer Biology; Cancer cells; Cell cycle; Cell Line, Tumor; Cell Proliferation; Clonal deletion; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - pathology; Deoxyribonucleic acid; DNA; DNA Damage; Gene deletion; Gene Expression Regulation; Genes; Genetic aspects; Genetics; Health aspects; Humans; Hypersensitivity; Laboratories; lncRNA; Matrin 3; Medical research; Metabolism; Methods; Nuclear Matrix-Associated Proteins - metabolism; p53; p53 Protein; PINCR; Proteins; Ribonucleic acid; RNA; RNA sequencing; RNA, Long Noncoding - metabolism; RNA-binding protein; RNA-Binding Proteins - metabolism; RP3-326I13.1; Software; Tumor Suppressor Protein p53 - metabolism; United States > US; RP3-326I13.1; lncRNA; DNA damage; Matrin 3; cancer biology; PINCR; human; p53
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.23244

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 (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) and tumor growth . Targeted deletion of in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including and . Using a novel RNA pulldown approach that utilized endogenous S1-tagged , we show that 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/ /Matrin 3 axis in response to DNA damage in CRC cells.