{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pekovic F"],"funding":["MWK","Martin Luther University","Ministry of Science, Research","Deutsche Forschungsgemeinschaft","National Cancer Institute","National Institutes of Health"],"pagination":["3950-3970"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10164591"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["51(8)"],"pubmed_abstract":["Posttranscriptional regulation of the maternal nanos mRNA is essential for the development of the anterior - posterior axis of the Drosophila embryo. The nanos RNA is regulated by the protein Smaug, which binds to Smaug recognition elements (SREs) in the nanos 3'-UTR and nucleates the assembly of a larger repressor complex including the eIF4E-T paralog Cup and five additional proteins. The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase. Here we report an in vitro reconstitution of the Drosophila CCR4-NOT complex and Smaug-dependent deadenylation. We find that Smaug by itself is sufficient to cause deadenylation by the Drosophila or human CCR4-NOT complexes in an SRE-dependent manner. CCR4-NOT subunits NOT10 and NOT11 are dispensable, but the NOT module, consisting of NOT2, NOT3 and the C-terminal part of NOT1, is required. Smaug interacts with the C-terminal domain of NOT3. Both catalytic subunits of CCR4-NOT contribute to Smaug-dependent deadenylation. Whereas the CCR4-NOT complex itself acts distributively, Smaug induces a processive behavior. The cytoplasmic poly(A) binding protein (PABPC) has a minor inhibitory effect on Smaug-dependent deadenylation. Among the additional constituents of the Smaug-dependent repressor complex, Cup also facilitates CCR4-NOT-dependent deadenylation, both independently and in cooperation with Smaug."],"journal":["Nucleic acids research"],"pubmed_title":["RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent deadenylation of the nanos mRNA in a reconstituted system."],"pmcid":["PMC10164591"],"funding_grant_id":["JE 827/1-1","INST 35/1314-1 FUGG","INST 35/1503–1 FUGG","WA 548/17-1","WA 548/16-1"],"pubmed_authors":["Metz J","Jeske M","Pekovic F","Rammelt C","Kubikova J","Wahle E"],"additional_accession":[]},"is_claimable":false,"name":"RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent deadenylation of the nanos mRNA in a reconstituted system.","description":"Posttranscriptional regulation of the maternal nanos mRNA is essential for the development of the anterior - posterior axis of the Drosophila embryo. The nanos RNA is regulated by the protein Smaug, which binds to Smaug recognition elements (SREs) in the nanos 3'-UTR and nucleates the assembly of a larger repressor complex including the eIF4E-T paralog Cup and five additional proteins. The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase. Here we report an in vitro reconstitution of the Drosophila CCR4-NOT complex and Smaug-dependent deadenylation. We find that Smaug by itself is sufficient to cause deadenylation by the Drosophila or human CCR4-NOT complexes in an SRE-dependent manner. CCR4-NOT subunits NOT10 and NOT11 are dispensable, but the NOT module, consisting of NOT2, NOT3 and the C-terminal part of NOT1, is required. Smaug interacts with the C-terminal domain of NOT3. Both catalytic subunits of CCR4-NOT contribute to Smaug-dependent deadenylation. Whereas the CCR4-NOT complex itself acts distributively, Smaug induces a processive behavior. The cytoplasmic poly(A) binding protein (PABPC) has a minor inhibitory effect on Smaug-dependent deadenylation. Among the additional constituents of the Smaug-dependent repressor complex, Cup also facilitates CCR4-NOT-dependent deadenylation, both independently and in cooperation with Smaug.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2025-04-05T09:12:01.431Z","creation":"2025-04-05T09:12:01.431Z"},"accession":"S-EPMC10164591","cross_references":{"pubmed":["36951092"],"doi":["10.1093/nar/gkad159"]}}