Effects of airborne particulate matter on alternative pre-mRNA splicing in colon cancer cells

Environ Res. 2015 Jul:140:185-90. doi: 10.1016/j.envres.2015.04.001. Epub 2015 Apr 9.

Abstract

Alternative pre-mRNA splicing plays key roles in determining tissue- and species-specific cell differentiation as well as in the onset of hereditary disease and cancer, being controlled by multiple post- and co-transcriptional regulatory mechanisms. We report here that airborne particulate matter, resulting from industrial pollution, inhibits expression and specifically affects alternative splicing at the 5' untranslated region of the mRNA encoding the bone morphogenetic protein BMP4 in human colon cells in culture. These effects are consistent with a previously reported role for BMP4 in preventing colon cancer development, suggesting that ingestion of particulate matter could contribute to the onset of colon cell proliferation. We also show that the underlying mechanism might involve changes in transcriptional elongation. This is the first study to demonstrate that particulate matter causes non-pleiotropic changes in alternative splicing.

Keywords: Air pollution; Alternative splicing; Bone morphogenetic protein; Colon cancer cells; Particulate matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects*
  • Base Sequence
  • Bone Morphogenetic Protein 4 / genetics
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • DNA Primers
  • HEK293 Cells
  • Humans
  • Particulate Matter / pharmacology*
  • RNA Precursors / genetics*
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Bone Morphogenetic Protein 4
  • DNA Primers
  • Particulate Matter
  • RNA Precursors
  • RNA, Messenger