Translation of Human β-Actin mRNA is Regulated by mTOR Pathway

Genes (Basel). 2019 Jan 29;10(2):96. doi: 10.3390/genes10020096.

Abstract

The mammalian target of rapamycin (mTOR) kinase is a well-known master regulator of growth-dependent gene expression in higher eukaryotes. Translation regulation is an important function of the mTORC1 pathway that controls the synthesis of many ribosomal proteins and translation factors. Housekeeping genes such as β-actin (ACTB) are widely used as negative control genes in studies of growth-dependent translation. Here we demonstrate that translation of both endogenous and reporter ACTB mRNA is inhibited in the presence of mTOR kinase inhibitor (Torin1) and under amino acid starvation. Notably, 5'UTR and promoter of ACTB are sufficient for the mTOR-dependent translational response, and the degree of mTOR-sensitivity of ACTB mRNA translation is cell type-dependent.

Keywords: 5’UTR; ACTB; amino acid starvation; mRNA; mTOR; translation regulation; β-actin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Actins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Naphthyridines / pharmacology
  • PC-3 Cells
  • Protein Biosynthesis / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one
  • Actins
  • Naphthyridines
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • TOR Serine-Threonine Kinases