PARP1-RNA interaction analysis: PARP1 regulates the expression of extracellular matrix-related genes in HK-2 renal proximal tubular epithelial cells

FEBS Lett. 2021 May;595(9):1375-1387. doi: 10.1002/1873-3468.14065. Epub 2021 Mar 20.

Abstract

Recent studies suggest that Poly(ADP-ribose) polymerase 1 (PARP1) acts as an RNA-binding protein in a majority of renal diseases with tubular cell injury. However, detailed knowledge of RNA targets and the RNA-binding regions for PARP1 is unknown. Herein, mapping of iRIP-seq reads in HK-2 renal tubular epithelial cells showed a biased distribution at coding sequence (CDS) and intron regions that is specific to these cells. A total of 1708 differentially expressed genes were identified after PARP1 knockdown using RNA-seq. Furthermore, transcriptome analysis also showed that selective variable splicing was globally regulated by PARP1 in HK-2 cells. By comparison of PARP1 RNA-seq and iRIP-seq data, we found 68 overlapping genes that are enriched in 'extracellular matrix' pathway. Follow-up identification of their interactions may contribute vital insights into the regulatory role of PARP1 as an RNA-binding protein in HK-2 cells.

Keywords: HK-2 cells; PARP1; RNA-seq; extracellular matrix; iRIP-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extracellular Matrix / genetics*
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Humans
  • Introns / genetics
  • Kidney / metabolism*
  • Kidney Tubules, Proximal / metabolism
  • Poly (ADP-Ribose) Polymerase-1 / genetics*
  • RNA / genetics
  • RNA Splicing / genetics
  • RNA-Binding Proteins / genetics*
  • RNA-Seq

Substances

  • RNA-Binding Proteins
  • RNA
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1