CNOT6

Last update 08 May 2025

Basic Info

Synonyms

Carbon catabolite repressor protein 4 homolog, CCR4, CCR4 carbon catabolite repression 4-like

+ [5]

Introduction

Poly(A) nuclease with 3'-5' RNase activity. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in mRNA decay mediated by the major-protein-coding determinant of instability (mCRD) of the FOS gene in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA. The increase of ligand-dependent ESR1-mediated transcription is much smaller, if any. Mediates cell proliferation and cell survival and prevents cellular senescence.

100 Clinical Results associated with CNOT6

100 Translational Medicine associated with CNOT6

0 Patents (Medical) associated with CNOT6

Literatures (Medical) associated with CNOT6

01 Feb 2025·The Journal of Pharmacology and Experimental Therapeutics

CNOT6L deadenylase suppresses cardiac remodeling in heart failure through downregulation of tenascin-C mRNA

Article

Author: Yamamoto, Tadashi ; Yamamoto, Ayaha ; Kuba, Keiji ; Hoshizaki, Midori ; Morita, Masahiro ; Suzuki, Toru ; Fujio, Yasushi ; Sato, Teruki ; Suzuki, Yutaka ; Watanabe, Hiroyuki ; Minato, Takafumi ; Imai, Yumiko ; Yamaguchi, Tomokazu

Heart failure is rapidly increasing and is a growing burden on human health and the economy in the world. The functional role of mRNA regulation in the pathogenesis of heart failure remains to be elucidated. Carbon catabolite repression 4-negative on TATA-less complex is a multisubunit protein complex that deadenylates mRNA, a process of exonuclease-mediated degradation of mRNA poly(A) tail. Here we show the cardiac protective roles of deadenylase subunit CNOT6L against cardiac stress. After 2 weeks of transverse aortic constriction (TAC)-induced pressure overload, expression of CNOT6L deadenylase subunit was significantly upregulated in the mouse hearts. When CNOT6L gene was genetically deleted, the mice exhibited marked decline of left ventricular contractility and enhancement of fibrosis at 2 weeks after TAC. Transcriptome analyses elucidated that CNOT6L targets tenascin-C mRNA, which stimulates tissue fibrosis and inflammation. CNOT6L deletion markedly upregulated tenascin-C expression in cardiac fibroblasts. Poly(A) tail length and luciferase reporter analyses revealed that CNOT6L catalyzes deadenylation of tenascin-C mRNA likely through interaction with the cis-element in its 3'-untranslated region. Double knockout of tenascin-C and CNOT6L ameliorated cardiac fibrosis and dysfunction in single CNOT6 knockout mice under TAC or chronic infusion of angiotensin II. Thus, CNOT6L deadenylase prevents the progression of heart failure through downregulation of the expression of tenascin-C in cardiac fibroblasts, implicating a potential therapeutic strategy of targeting mRNA deadenylation. SIGNIFICANCE STATEMENT: To our knowledge, this study provides the first evidence that posttranscriptional regulation of tenascin-C expression in cardiac fibroblasts, including cell-type-specific roles of CNOT6L-mediated mRNA deadenylation, is crucial to maintain heart functions against pressure overload stress or angiotensin II-induced hypertension, implicating a potential therapeutic strategy of targeting mRNA deadenylation.

02 Dec 2024·The Plant Cell

The potato RNA metabolism machinery is targeted by the cyst nematode effector RHA1B for successful parasitism

Article

Author: Ramirez, Chloe ; Caplan, Allan ; Kuhl, Joseph C ; Huang, Li ; Zhang, Cankui ; Xiao, Fangming ; Kud, Joanna ; Xia, Chao ; Dandurand, Louise-Marie ; Yuan, Yulin

AbstractThe potato (Solanum tuberosum) cyst nematode Globodera pallida induces a multinucleate feeding site (syncytium) in potato roots as its sole source of nutrition. Here, we demonstrate that the G. pallida effector RING-H2 finger A1b (RHA1B), which is a functional ubiquitin ligase, interferes with the carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) deadenylase-based RNA metabolism machinery that regulates syncytium development in G. pallida-infected potato. Specifically, RHA1B targets the CCR4-associated factor 1 (CAF1) and StNOT10 subunits of the CCR4-NOT complex for proteasome-mediated degradation, leading to upregulation of the cyclin gene StCycA2 involved in syncytium formation. The StCAF1 subunit of CCR4-NOT recruits the RNA binding protein StPUM5 to deadenylate StCycA2 mRNA, resulting in shortened poly-A tails of StCycA2 mRNA and subsequently reduced transcript levels. Knockdown of either subunit (StCAF1 or StNOT10) of the CCR4-NOT complex or StPUM5 in transgenic potato plants resulted in enlarged syncytia and enhanced susceptibility to G. pallida infection, which resembles the phenotypes of StCycA2 overexpression transgenic potato plants. Genetic analyses indicate that transgenic potato plants overexpressing RHA1B exhibit similar phenotypes as transgenic potato plants with knockdown of StNOT10, StCAF1, or StPUM5. Thus, our data suggest that G. pallida utilizes the RHA1B effector to manipulate RNA metabolism in host plants, thereby promoting syncytium development for parasitic success.

01 Feb 2024·New Phytologist

The CARBON CATABOLITE REPRESSION 4A‐mediated RNA deadenylation pathway acts on the transposon RNAs that are not regulated by small RNAs

Article

Author: Lei, Zhen ; Cho, Jungnam ; Li, Hui ; Jeong, Dong‐Hoon ; Wang, Ling

Summary

Transposable elements (TEs) are mobile genetic elements that can impair the host genome stability and integrity. It has been well documented that activated transposons in plants are suppressed by small interfering (si) RNAs. However, transposon repression by the cytoplasmic RNA surveillance system is unknown.

Here, we show that mRNA deadenylation is critical for controlling transposons in Arabidopsis. Trimming of poly(A) tail is a rate‐limiting step that precedes the RNA decay and is primarily mediated by the CARBON CATABOLITE REPRESSION 4 (CCR4)‐NEGATIVE ON TATA‐LESS (NOT) complex.

We found that the loss of CCR4a leads to strong derepression and mobilization of TEs in Arabidopsis. Intriguingly, CCR4a regulates a largely distinct set of TEs from those controlled by RNA‐dependent RNA Polymerase 6 (RDR6), a key enzyme that produces cytoplasmic siRNAs. This indicates that the cytoplasmic RNA quality control mechanism targets the TEs that are poorly recognized by the previously well‐characterized RDR6‐mediated pathway, and thereby augments the host genome stability.

Our study suggests a hitherto unknown mechanism for transposon repression mediated by RNA deadenylation and unveils a complex nature of the host's strategy to maintain the genome integrity.

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CNOT6

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