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

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L. V. Putlyaeva¹, A. M. Schwartz¹, K. V. Korneev^1,2, M. Covic¹, L. A. Uroshlev^1,3, V. Yu. Makeev^1,3, S. E. Dmitriev^1,4, and D. V. Kuprash^1,2*

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

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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.

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KEY WORDS: protein biosynthesis, translation control, uORF, mRNA

DOI: 10.1134/S0006297914120165

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