Structural basis for inhibition of the deadenylase activity of human <scp>CNOT</scp>6L

Zhang, Qionglin; Yan, Dongke; Guo, E.Z.; Ding, Bojian; Yang, Wen; Liu, Ruihua; Yamamoto, Tadashi; Bartlam, Mark

doi:10.1002/1873-3468.12160

Cited by 13 publications

(13 citation statements)

References 30 publications

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“…Small molecules that inhibit CAF1 deadenylase activity have recently been reported for human CAF1 Maryati et al, 2014Maryati et al, , 2015Zhang et al, 2016). Because these inhibitors are not commercially available, we have synthesized a series of pyrazolo[4,3-d]-pyrimidine and quinazoline derivatives with the purpose of finding novel CAF1 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Role of the Citrus sinensis RNA deadenylase CsCAF1 in citrus canker resistance

Shimo

Terassi

Silva

et al. 2019

Molecular Plant Pathology

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Summary Poly(A) tail shortening is a critical step in messenger RNA (mRNA) decay and control of gene expression. The carbon catabolite repressor 4 (CCR4)‐associated factor 1 (CAF1) component of the CCR4‐NOT deadenylase complex plays an essential role in mRNA deadenylation in most eukaryotes. However, while CAF1 has been extensively investigated in yeast and animals, its role in plants remains largely unknown. Here, we show that the Citrus sinensis CAF1 (CsCAF1) is a magnesium‐dependent deadenylase implicated in resistance against the citrus canker bacteria Xanthomonas citri . CsCAF1 interacted with proteins of the CCR4‐NOT complex, including CsVIP2, a NOT2 homologue, translin‐associated factor X (CsTRAX) and the poly(A)‐binding proteins CsPABPN and CsPABPC. CsCAF1 also interacted with PthA4, the main X. citri effector required for citrus canker elicitation. We also present evidence suggesting that PthA4 inhibits CsCAF1 deadenylase activity in vitro and stabilizes the mRNA encoded by the citrus canker susceptibility gene CsLOB1 , which is transcriptionally activated by PthA4 during canker formation. Moreover, we show that an inhibitor of CsCAF1 deadenylase activity significantly enhanced canker development, despite causing a reduction in PthA4‐dependent CsLOB1 transcription. These results thus link CsCAF1 with canker development and PthA4‐dependent transcription in citrus plants.

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Section: Discussionmentioning

confidence: 99%

Role of the Citrus sinensis RNA deadenylase CsCAF1 in citrus canker resistance

Shimo

Terassi

Silva

et al. 2019

Molecular Plant Pathology

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“…The data suggest a model where the two aspartic residues (D287 and D346) are in close proximity in the reaction very dependent on the 3D conformation of the full enzyme that is absolutely essential to be conserved in order to coordinate the four catalytic residues in the exact optimal spatial positions in the proximity of the catalytic site of AtHESPERIN to achieve maximal efficacy. 3C) and may indicate the displacement of Mg 2+ from the active site could account for loss of activity as has been shown for CNOT6L (12).…”

Section: Accepted Articlementioning

confidence: 70%

“…DEDD nucleases are named after conserved Asp (D) and Glu (E) residues in their active site. EEP (exonuclease-endonuclease-phosphatase) nucleases have conserved catalytic Asp, Glu and His residues (5,10,11), which are important for Mg 2+ coordination and contribute to substrate positioning within the catalytic pocket (12).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and in silico identification of the active site and the catalytic mechanism of the circadian deadenylase HESPERIN

et al. 2022

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The 24 h molecular clock is based on the stability of rhythmically expressed transcripts. The shortening of the poly(A) tail of mRNAs is often the first and rate-limiting step that determines the lifespan of a mRNA and is catalyzed by deadenylases. Herein, we determine the catalytic site of Hesperin, a recently described circadian deadenylase in plants, using a modified site-directed mutagenesis protocol and a custom vector, pATHRA. To explore the catalytic efficiency of AtHESPERIN we investigated the effect of AMP and neomycin, and utilized molecular modelling simulations to propose a catalytic mechanism. Collectively, the biochemical and in silico results classify AtHESPERIN in the EEP deadenylase superfamily and contribute to the understanding of the intricate mechanisms of circadian mRNA turnover.

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“…The addition of adenosine monophosphate (AMP) can inhibit deadenylation of the poly(A) tail for nuclear transcripts by potently inhibiting the major deadenylase CNOT6L and CNOT7 27 , leading us to ask whether the poly(A) tail length of MT-mRNAs was affected by adding AMP. Our results demonstrated that AMP addition did not affect the distribution of MT-mRNA in the poly(A) tail length in both mouse metaphase II (MII) oocytes and mouse 2-cell embryos (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dynamics of mitochondrial mRNA abundance and poly(A) tail during the mammalian oocyte-to-embryo transition

Liu

Zhang

et al. 2021

Preprint

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Mitochondria are responsible for producing a cell energy and play a central role in many metabolic tasks, as well as signaling transduction and cell death. Mitochondria dysfunctions cause several human diseases and aging processes. Mammalian oocytes contain far more mitochondria than somatic cells. The nuclear localization of mitochondrial tricarboxylic acid cycle (TCA) cycle enzymes, which normally localize in the mitochondria, is critical for zygotic genome activation (ZGA) and the oocyte-to-embryo transition (OET) in mice. However, during the mammalian OET, the abundance and post-transcriptional regulation of mitochondrial mRNA (MT-mRNA), particularly the poly(A) tail, has never been studied. Here, we used two independent sequencing methods (PAIso-seq1 and PAIso-seq2) to describe the features of MT-mRNA in mouse cell lines, thirteen mouse tissues and during the OET in mouse, rat, pig, and humans. These features included expression abundance, poly(A) tail length, and non-A residues in poly(A) tails. Unlike nuclear mRNA, we discovered that MT-mRNA has a stable distribution pattern of poly(A) tail length in different cell lines, across tissues, and during mammalian OET. MT-mRNA possesses non-A residues in the poly(A) tail (non-A residues hereafter), which change slightly across tissues and during the OET. We also found that the abundance of MT-mRNA varies substantially across tissues, increases during the OET, and increases along major ZGA in mice, rats, pigs, and humans. These findings provide insights into changes in MT-mRNA abundance and poly(A) tail during the mammalian OET and provide a resource for future studies on the posttranscriptional regulation of mitochondrial transcripts

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Structural basis for inhibition of the deadenylase activity of human CNOT6L

Cited by 13 publications

References 30 publications

Role of the Citrus sinensis RNA deadenylase CsCAF1 in citrus canker resistance

Role of the Citrus sinensis RNA deadenylase CsCAF1 in citrus canker resistance

Biochemical and in silico identification of the active site and the catalytic mechanism of the circadian deadenylase HESPERIN

Dynamics of mitochondrial mRNA abundance and poly(A) tail during the mammalian oocyte-to-embryo transition

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