Mammalian Smaug is a translational repressor that forms cytoplasmic foci similar to stress granules.
Cytoplasmic events depending on RNA-binding proteins contribute to the fine-tuning of gene expression. Sterile alpha motif-containing RNA-binding proteins constitute a novel family of post-transcriptional regulators that recognize a specific RNA sequence motif known as Smaug recognition element (SRE). The Drosophila member of this family, dSmaug, triggers the translational repression and deadenylation of maternal mRNAs by independent mechanisms, and the yeast homologue Vts1 stimulates degradation of SRE-containing messengers. Two homologous genes are present in the mammalian genome. Here we showed that hSmaug 1, encoded in human chromosome 14, represses the translation of reporter transcripts carrying SRE motifs. When expressed in fibroblasts, hSmaug 1 forms cytoplasmic granules that contain polyadenylated mRNA and the RNA-binding proteins Staufen, TIAR, TIA-1, and HuR. Smaug 1 foci are distinct from degradation foci. The murine protein mSmaug 1 is expressed in the central nervous system and is abundant in post-synaptic densities, a subcellular region where translation is tightly regulated by synaptic stimulation. Biochemical analysis indicated that mSmaug 1 is present in synaptoneurosomal 20 S particles. These results suggest a role for mammalian Smaug 1 in RNA granule formation and translation regulation in neurons.
Baez
María V
MV
Fundación Instituto Leloir, IIBBA CONICET and IIB Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, C1405BWE Buenos Aires, Argentina.
Boccaccio
Graciela L
GL
D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002490:Central Nervous System; D002522:Chlorocebus aethiops; D002883:Chromosomes, Human, Pair 14 / Q000378:metabolism; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011132:Polyribosomes / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D018076:DNA, Complementary; D029721:Drosophila Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C507993:SAMD4A protein, human; C507994:Smaug1 protein, mouse; C402587:smg protein, Drosophila; D012313:RNA; D008156:Luciferases