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Upstream Open Reading Frames Regulate Translation of the Long Isoform of SLAMF1 mRNA That Encodes Costimulatory Receptor CD150

L. V. Putlyaeva1, A. M. Schwartz1, K. V. Korneev1,2, M. Covic1, L. A. Uroshlev1,3, V. Yu. Makeev1,3, S. E. Dmitriev1,4, and D. V. Kuprash1,2*

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; E-mail: kuprash@gmail.com

2Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

3Vavilov Institute of General Genetics, Russian Academy of Sciences, ul. Gubkina 3, 119991 Moscow, Russia

4Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

* To whom correspondence should be addressed.

Received June 30, 2014
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

DOI: 10.1134/S0006297914120165