Biochemistry (Moscow)

, Volume 79, Issue 12, pp 1405–1411 | Cite as

Upstream open reading frames regulate translation of the long isoform of SLAMF1 mRNA that encodes costimulatory receptor CD150

  • L. V. Putlyaeva
  • A. M. Schwartz
  • K. V. Korneev
  • M. Covic
  • L. A. Uroshlev
  • V. Yu. Makeev
  • S. E. Dmitriev
  • D. V. Kuprash
Article

Abstract

More than 40% of human genes contain upstream open reading frames (uORF) in their 5′-untranslated regions (5′-UTRs) and at the same time express at least one truncated mRNA isoform containing no uORF. We studied translational regulation by four uORFs found in the 5′-UTR of full-length mRNA for SLAMF1, the gene encoding CD150 membrane protein. CD150 is a member of the CD2 superfamily, a costimulatory lymphocyte receptor, a receptor for measles virus, and a microbial sensor on macrophages. The SLAMF1 gene produces at least two mRNA isoforms that differ in their 5′-UTRs. In the long isoform of the SLAMF1 mRNA that harbors four uORFs in the 5′-UTR, the stop codon of uORF4 overlaps with the AUG codon of the main ORF forming a potential termination-reinitiation site UGAUG, while uORF2 and uORF3 start codons flank a sequence identical to Motif 1 from the TURBS regulatory element. TURBS was shown to be required for a coupled termination-reinitiation event during translation of polycistronic RNAs of some viruses. In a model cell system, reporter mRNA based on the 5′-UTR of SLAMF1 short isoform, which lacks any uORF, is translated 5–6 times more efficiently than the mRNA with 5′-UTR from the long isoform. Nucleotide substitutions disrupting start codons in either uORF2-4 result in significant increase in translation efficiency, while substitution of two nucleotides in TURBS Motif 1 leads to a 2-fold decrease in activity. These data suggest that TURBS-like elements can serve for translation control of certain cellular mRNAs containing uORFs.

Key words

protein biosynthesis translation control uORF mRNA 

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Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • L. V. Putlyaeva
    • 1
  • A. M. Schwartz
    • 1
  • K. V. Korneev
    • 1
    • 2
  • M. Covic
    • 1
  • L. A. Uroshlev
    • 1
    • 3
  • V. Yu. Makeev
    • 1
    • 3
  • S. E. Dmitriev
    • 1
    • 4
  • D. V. Kuprash
    • 1
    • 2
  1. 1.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia
  2. 2.Faculty of BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  4. 4.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia

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