MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation

Mol Cell. 2008 May 23;30(4):460-71. doi: 10.1016/j.molcel.2008.05.001.

Abstract

MicroRNAs (miRNAs) are small RNAs that function as posttranscriptional regulators of gene expression. miRNAs affect a variety of signaling pathways, and impaired miRNA regulation may contribute to the development of cancer and other diseases. Here we show that miRNA miR-10a interacts with the 5' untranslated region of mRNAs encoding ribosomal proteins to enhance their translation. miR-10a alleviates translational repression of the ribosomal protein mRNAs during amino acid starvation and is required for their translational induction following anisomycin treatment or overexpression of RAS. We show that miR-10a binds immediately downstream of the regulatory 5'TOP motif and that the 5'TOP regulatory complex and miR-10a are functionally interconnected. The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Amino Acids / metabolism
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Transformation, Neoplastic
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Protein Biosynthesis*
  • Rats
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism

Substances

  • 5' Untranslated Regions
  • Amino Acids
  • LILRB2 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Ribosomal Proteins