CCR4-Associated Factor CAF1 Is an Essential Factor for Spermatogenesis

Berthet, Cyril; Morera, A.M.; Asensio, Marie-Jeanne; Chauvin, Marie-Agnès; Morel, Anne-Pierre; Dijoud, Frédérique; Magaud, Jean‐Pierre; Durand, Philippe; Rouault, Jean‐Pierre

doi:10.1128/mcb.24.13.5808-5820.2004

Cited by 89 publications

(84 citation statements)

References 82 publications

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“…During the mid-phase of spermiogenesis, the spermatid nucleus moves toward the periphery of the cell surface and comes very close to the Sertoli cell (Russell, 1993). They then form an an intimate intercellular connection like tubulobulbar complex (Russell, 1993 (Nakamura et al, 2004;Berthet et al, 2004). This demonstrated that the absence of the Cnot7 gene in haploid cells does not impair the final step of spermiogenesis leading to fertile spermatozoa.…”

Section: Cnot7mentioning

confidence: 91%

Abnormal sperm morphology caused by defects in Sertoli cells of Cnot7 knockout mice

Ogawa

Ito

Nakamura

et al. 2004

Archives of Histology and Cytology

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Section: Cnot7mentioning

confidence: 91%

Abnormal sperm morphology caused by defects in Sertoli cells of Cnot7 knockout mice

Ogawa

Ito

Nakamura

et al. 2004

Archives of Histology and Cytology

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“…For example, Drosophila CCR4 is crucial in oocytes for early stages of oogenesis (Morris et al, 2005;Zaessinger et al, 2006) and one of the two mammalian CAF-1 homologs, CNOT7, is essential in Sertoli cells to support mouse spermatogenesis (Berthet et al, 2004;Nakamura et al, 2004). In C. elegans, genetic elimination of ccf-1 or ntl-1 activity precludes an assessment of gonadal defects in the adult.…”

Section: Discussionmentioning

confidence: 99%

The Ccr4-Not deadenylase complex constitutes the major poly(A) removal activity inC. elegans

Nousch

Techritz

Hampel

et al. 2013

Journal of Cell Science

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SummaryPost-transcriptional regulatory mechanisms are widely used to control gene expression programs of tissue development and physiology. Controlled 39 poly(A) tail-length changes of mRNAs provide a mechanistic basis of such regulation, affecting mRNA stability and translational competence. Deadenylases are a conserved class of enzymes that facilitate poly(A) tail removal, and their biochemical activities have been mainly studied in the context of single-cell systems. Little is known about the different deadenylases and their biological role in multicellular organisms. In this study, we identify and characterize all known deadenylases of Caenorhabditis elegans, and identify the germ line as tissue that depends strongly on deadenylase activity. Most deadenylases are required for hermaphrodite fertility, albeit to different degrees. Whereas ccr-4 and ccf-1 deadenylases promote germline function under physiological conditions, panl-2 and parn-1 deadenylases are only required under heat-stress conditions. We also show that the Ccr4-Not core complex in nematodes is composed of the two catalytic subunits CCR-4 and CCF-1 and the structural subunit NTL-1, which we find to regulate the stability of CCF-1. Using bulk poly(A) tail measurements with nucleotide resolution, we detect strong deadenylation defects of mRNAs at the global level only in the absence of ccr-4, ccf-1 and ntl-1, but not of panl-2, parn-1 and parn-2. Taken together, this study suggests that the Ccr4-Not complex is the main deadenylase complex in C. elegans germ cells. On the basis of this and as a result of evidence in flies, we propose that the conserved Ccr4-Not complex is an essential component in post-transcriptional regulatory networks promoting animal reproduction.

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“…These mice have a normal appearance, although males are sterile because of a defect in spermatogenesis (Berthet et al, 2004;Nakamura et al, 2004). In addition, Cnot7 mice display an increased bone mass caused by elevated osteoblast activity because of enhanced BMP signaling (Washio-Oikawa et al, 2007).…”

Section: The Cnot7 and Cnot8 Paralogues Display Overlapping Functionsmentioning

confidence: 99%

The Ccr4–Not Deadenylase Subunits CNOT7 and CNOT8 Have Overlapping Roles and Modulate Cell Proliferation

Aslam

Mittal

Koch

et al. 2009

MBoC

103

115

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Accurate gene expression requires the precise control of mRNA levels, which are determined by the relative rates of nuclear (pre-)mRNA synthesis and processing, and cytoplasmic mRNA turnover. A key step in mRNA degradation is the removal of the poly(A) tail, which involves several deadenylases including components of the Ccr4 -Not complex. Here, we focused on the role of the human paralogues CNOT7 (hCaf1/Caf1a) and CNOT8 (hPop2/Caf1b/Calif), which possess deadenylase activity mediated by DEDD nuclease domains. We show that efficient proliferation requires both subunits, although combined knockdown of CNOT7 and CNOT8 further reduces cell proliferation indicating partial redundancy between these proteins. Interestingly, the function of CNOT7 in cell proliferation partly depends on its catalytic activity. On the other hand, the interaction between CNOT7 and BTG2, a member of the antiproliferative BTG/Tob family involved in transcription and mRNA decay appears less important for proliferation of MCF7 cells, suggesting that CNOT7 does not function solely in conjunction with BTG2. Further analysis of gene expression profiles of CNOT7 and/or CNOT8 knockdown cells underscores the partial redundancy between these subunits and suggests that regulation of several genes, including repression of the antiproliferative genes MSMB and PMP22, by the Ccr4 -Not complex contributes to cell proliferation. INTRODUCTIONAccurate gene expression requires the precise control of mRNA levels that are determined by the relative rates of (pre-)mRNA synthesis and processing, and by mRNA turnover. Degradation of eukaryotic mRNA is initiated by the shortening and removal of the poly(A) tail by at least two different complexes containing distinct deadenylase subunits (Parker and Song, 2004;Garneau et al., 2007;Goldstrohm and Wickens, 2008). In both yeast and human cells, initial shortening of the poly(A) tail is carried out by Pan2, which forms a heterodimer with Pan3 (Brown et al., 1996;Boeck et al., 1998;Brown and Sachs, 1998;Uchida et al., 2004). Subsequent removal of poly(A) residues is achieved by Ccr4 -Not, a conserved complex, which contains about 10 subunits, including several deadenylase components (Tucker et al., 2001;Temme et al., 2004;Yamashita et al., 2005). The yeast Ccr4 protein and its human orthologues CNOT6 (hCcr4/Ccr4a) and CNOT6L (hCcr4-like/Ccr4b) contain an exonuclease/endonuclease/ phosphatase (EEP) domain that is responsible for the RNA nuclease activity (Dupressoir et al., 2001;Chen et al., 2002;Tucker et al., 2002;Morita et al., 2007). In addition, these proteins interact via leucine-rich motifs with yeast Caf1 (Pop2) or its human orthologues CNOT7 (hCaf1/Caf1a) and CNOT8 (hPop2/Caf1b/Calif), which contain RNA nuclease activities attributed to DEDD domains (Daugeron et al., 2001;Dupressoir et al., 2001;Clark et al., 2004;Viswanathan et al., 2004;Bianchin et al., 2005). The CNOT7 and CNOT8 proteins interact with members of the BTG/Tob family of antiproliferative proteins, which are implicated in mRNA turnover (Ezzeddine ...

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CCR4-Associated Factor CAF1 Is an Essential Factor for Spermatogenesis

Cited by 89 publications

References 82 publications

Abnormal sperm morphology caused by defects in Sertoli cells of Cnot7 knockout mice

Abnormal sperm morphology caused by defects in Sertoli cells of Cnot7 knockout mice

The Ccr4-Not deadenylase complex constitutes the major poly(A) removal activity inC. elegans

The Ccr4–Not Deadenylase Subunits CNOT7 and CNOT8 Have Overlapping Roles and Modulate Cell Proliferation

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