HELZ directly interacts with CCR4–NOT and causes decay of bound mRNAs
| Autor: | Dipankar Bhandari, Ramona Weber, Tobias Raisch, Cátia Igreja, Maria Fauser, Aoife Hanet, Duygu Kuzuoğlu-Öztürk, Vincenzo Ruscica, Chung Te Chang, Felix Räsch, Lara Wohlbold |
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| Rok vydání: | 2019 |
| Předmět: |
endocrine system
Receptors CCR4 RNA Stability Health Toxicology and Mutagenesis TATA box Catabolite repression Repressor Plant Science Nervous System Biochemistry Genetics and Molecular Biology (miscellaneous) Cell Line 03 medical and health sciences 0302 clinical medicine Transcription (biology) Protein biosynthesis Animals Humans Research Articles 030304 developmental biology Regulation of gene expression 0303 health sciences Ecology biology Chemistry Gene Expression Profiling Gene Expression Regulation Developmental Helicase biology.organism_classification TATA Box Cell biology Drosophila melanogaster HEK293 Cells Protein Biosynthesis biology.protein RNA Helicases 030217 neurology & neurosurgery Protein Binding Research Article |
| Zdroj: | Life Science Alliance |
| ISSN: | 2575-1077 |
| Popis: | The putative UPF1-like SF1 helicase HELZ directly interacts with the CCR4–NOT deadenylase complex to induce translational repression and 5′-to-3′ decay of bound mRNAs. Eukaryotic superfamily (SF) 1 helicases have been implicated in various aspects of RNA metabolism, including transcription, processing, translation, and degradation. Nevertheless, until now, most human SF1 helicases remain poorly understood. Here, we have functionally and biochemically characterized the role of a putative SF1 helicase termed “helicase with zinc-finger,” or HELZ. We discovered that HELZ associates with various mRNA decay factors, including components of the carbon catabolite repressor 4-negative on TATA box (CCR4–NOT) deadenylase complex in human and Drosophila melanogaster cells. The interaction between HELZ and the CCR4–NOT complex is direct and mediated by extended low-complexity regions in the C-terminal part of the protein. We further reveal that HELZ requires the deadenylase complex to mediate translational repression and decapping-dependent mRNA decay. Finally, transcriptome-wide analysis of Helz-null cells suggests that HELZ has a role in the regulation of the expression of genes associated with the development of the nervous system. |
| Databáze: | OpenAIRE |
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