HELZ directly interacts with CCR4-NOT and causes decay of bound mRNAs.
Aoife HanetFelix RäschRamona WeberVincenzo RuscicaMaria FauserTobias RaischDuygu Kuzuoğlu-ÖztürkChung-Te ChangDipankar BhandariCatia IgrejaLara WohlboldPublished in: Life science alliance (2019)
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.
Keyphrases
- binding protein
- induced apoptosis
- endothelial cells
- cell cycle arrest
- dendritic cells
- drosophila melanogaster
- regulatory t cells
- single cell
- genome wide
- transcription factor
- poor prognosis
- gene expression
- endoplasmic reticulum stress
- pluripotent stem cells
- oxidative stress
- immune response
- dna methylation
- small molecule
- cell proliferation
- amino acid
- protein protein