Role of Arginine Methylation in Alternative Polyadenylation of VEGFR-1 (Flt-1) pre-mRNA

Int J Mol Sci. 2020 Sep 4;21(18):6460. doi: 10.3390/ijms21186460.

Abstract

Mature mRNA is generated by the 3' end cleavage and polyadenylation of its precursor pre-mRNA. Eukaryotic genes frequently have multiple polyadenylation sites, resulting in mRNA isoforms with different 3'-UTR lengths that often encode different C-terminal amino acid sequences. It is well-known that this form of post-transcriptional modification, termed alternative polyadenylation, can affect mRNA stability, localization, translation, and nuclear export. We focus on the alternative polyadenylation of pre-mRNA for vascular endothelial growth factor receptor-1 (VEGFR-1), the receptor for VEGF. VEGFR-1 is a transmembrane protein with a tyrosine kinase in the intracellular region. Secreted forms of VEGFR-1 (sVEGFR-1) are also produced from the same gene by alternative polyadenylation, and sVEGFR-1 has a function opposite to that of VEGFR-1 because it acts as a decoy receptor for VEGF. However, the mechanism that regulates the production of sVEGFR-1 by alternative polyadenylation remains poorly understood. In this review, we introduce and discuss the mechanism of alternative polyadenylation of VEGFR-1 mediated by protein arginine methylation.

Keywords: PRMTs; VEGF; VEGFR-1; alternative polyadenylation; angiogenesis; arginine methylation; poly(A) signal; sVEGFR-1.

Publication types

  • Review

MeSH terms

  • Arginine / metabolism
  • Methylation
  • Polyadenylation / genetics*
  • RNA Precursors / metabolism
  • RNA Stability / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • RNA Precursors
  • RNA, Messenger
  • Arginine
  • Vascular Endothelial Growth Factor Receptor-1