AI Article Synopsis
Article Abstract
Human CNOT6L/CCR4, a member of the endonuclease-exonuclease-phosphatase (EEP) family enzymes, is one of the two deadenylase enzymes in the conserved CCR4-NOT complex. Here, we report inhibitor-bound crystal structures of the human CNOT6L nuclease domain in complex with the nucleotide CMP and the aminoglycoside neomycin. Deadenylase activity assays show that nucleotides are effective inhibitors of both CNOT6L and CNOT7, with AMP more effective than other nucleotides, and that neomycin is a weak deadenylase inhibitor. Structural analysis shows that all inhibitors occupy the substrate and magnesium-binding sites of CNOT6L, suggesting that inhibitors compete with both substrate and divalent magnesium ions for overlapping binding sites.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/1873-3468.12160 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Knockdown of CNOT3, a subunit of the CCR4-NOT deadenylase complex, sensitizes A549 human non-small cell lung cancer cells to senescence-inducing stimuli.
Biochem Biophys Res Commun
January 2025
Membranology Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa, 904-0495, Japan. Electronic address:
Cellular senescence is an essentially irreversible cell cycle arrest associated with upregulated inflammatory responses that contribute to various pathological and physiological processes, including aging, cancer, and cancer prevention. However, the underlying mechanisms are not fully understood. Here, we show that the downregulation of CNOT3, a subunit of the CCR4-NOT complex that deadenylates mRNA poly(A) tails, promotes cellular senescence in subpopulation of A549 human non-small cell lung cancer cells.
View Article and Find Full Text PDFMARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA.
Nat Commun
January 2025
Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Article Synopsis
- The study focuses on the role of a newly discovered protein family called MARTRE in regulating the poly(A) tail length of maternal mRNA during early embryo development in mice.
- MARTRE proteins inhibit the deadenylase CCR4-NOT, helping to maintain longer poly(A) tails and enhance mRNA translation efficiency.
- Deleting the Martre genes leads to shortened poly(A) tails, reduced mRNA translation, and delays in early embryonic development, emphasizing the importance of MARTRE in the translation of maternal mRNA.
mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation.
Cell Rep
December 2024
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Division of Genetic Medicine, Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address:
Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and uncommitted intermediate neural progenitors (immature INPs). We identify ubiquitin-specific protease 5 (Usp5) as a candidate Brat interactor essential for the degradation of Brat target mRNAs.
View Article and Find Full Text PDFThe effector PieF modulates mRNA stability through association with eukaryotic CCR4-NOT.
mSphere
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Unlabelled: The eukaryotic CCR4-NOT deadenylase complex is a highly conserved regulator of mRNA metabolism that influences the expression of the complete transcriptome, representing a prime target for a generalist bacterial pathogen. We show that a translocated bacterial effector protein, PieF (Lpg1972) of , directly interacts with the CNOT7/8 nuclease module of CCR4-NOT, with a dissociation constant in the low nanomolar range. PieF is a robust inhibitor of the DEDD-type nuclease, CNOT7, acting in a stoichiometric, dose-dependent manner.
View Article and Find Full Text PDFTOE1 deadenylase inhibits gastric cancer cell proliferation by regulating cell cycle progression.
Biochim Biophys Acta Gen Subj
January 2025
Beijing International Science and Technology Cooperation Base of Antivirus Drug, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China. Electronic address:
TOE1, also known as hCaf1z, belongs to the DEDD superfamily of deadenylases and a newly identified isoenzyme of hCaf1 deadenylases. Previous research has demonstrated that TOE1 has deadenylase activity, which can catalyze the degradation of poly(A) substrates and interact with hCcr4d to form the unconventional human Ccr4-Caf1 deadenylase complex. Our recent research indicates that hCaf1a and hCaf1b isoenzymes, highly expressed in gastric cancer, promote gastric cancer cell proliferation and tumorigenicity via modulating cell cycle progression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!