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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere23244
JournaleLife
Volume6
DOIs
Publication statusPublished - 5 Jun 2017
Externally publishedYes

Fingerprint

Long Noncoding RNA
Untranslated RNA
Colorectal Neoplasms
Cells
DNA Damage
Neoplasms
RNA-Binding Proteins
DNA
Tumors
Hypersensitivity
Genes
RNA
Apoptosis
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

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

In: eLife, Vol. 6, e23244, 05.06.2017.

Research output: Contribution to journalArticle

Chaudhary, R, Gryder, B, Woods, WS, Subramanian, M, Jones, MF, Li, XL, Jenkins, LM, Shabalina, SA, Mo, M, Dasso, M, Yang, Y, Wakefield, LM, Zhu, Y, Frier, SM, Moriarity, BS, Prasanth, KV, Perez-Pinera, P & Lal, A 2017, 'Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3', eLife, vol. 6, e23244. https://doi.org/10.7554/eLife.23244
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. / Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3. In: eLife. 2017 ; Vol. 6.
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