Evidence for translational repression of the SOCS-1 major open reading frame by an upstream open reading frame.
The suppressor of cytokine signalling 1 protein (SOCS-1) belongs to a novel family of cytokine inducible factors which function as inhibitors of the JAK/STAT pathway. While SOCS-1 previously has been described as a single-exon gene, here we present evidence for an additional 5' exon, separated by a 509 bp intron from exon 2. Exon 1 and part of exon 2 contain an open reading frame of 115 nt, ending one nucleotide upstream of the major reading frame. Using SOCS-1-promoter/luciferase constructs, we investigated which sequences are involved in the regulation of SOCS-1 expression. Serial promoter deletion clones indicate the localization and functionality of SP1, interferon-stimulated responsive elements (ISRE), and interferon-gamma-activated sites (GAS) promoter elements in the SOCS-1 5' flanking region. We present evidence that the upstream open reading frame (uORF) represses the translation of the downstream major open reading frame (mORF). Mutating the start codon of the uORF relieves this repression. Our data indicate that expression of the SOCS-1 protein is repressed on translational level by a mechanism, which bears similarities to that postulated for genes like retinoic acid receptor beta2 (RARbeta2), S-adenosylmethionine-decarboxylase (AdoMetDC), Bcl-2, and others.
Schlüter
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Institute of Human Genetics, University of Göttingen, Heinrich-Düker-Weg 12, Göttingen, 37073, Germany. gschlue@gwdg.de
Boinska
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Nieman-Seyde
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D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D002352:Carrier Proteins; D018076:DNA, Complementary; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins