Interaction between Not1p, a Component of the Ccr4-Not Complex, a Global Regulator of Transcription, and Dhh1p, a Putative RNA Helicase

Maillet, Laurent; Collart, Martine A.

doi:10.1074/jbc.m107979200

Cited by 91 publications

(88 citation statements)

References 25 publications

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“…The RNA-helicase Dhh1 binds many Lsm domain proteins and forms part of complexes involved in mRNA decapping, deadenylation and subsequent decay. [34][35][36] In addition, the association of Pbp1 and Lsm12 suggests that the Lsm domains of both proteins may assemble as heteromers as it is known from many other Lsm domain proteins. 20 Taken the length of about 722 and 1312 amino acid residues, respectively, into account, Pbp1 and ATX2 may form part of large complexes and work as scaffolding proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The map indicates that Pbp1 binds the DEAD/H-box RNAhelicase Dhh1 that plays a major role in mRNA turnover and degradation. [34][35][36] Furthermore, Pbp1 is clearly linked to the nuclear export machinery of mRNA 37 by the exportin Crm1 38 and the nucleoporin Nup145. 39 These findings match experimental results that observed Crm1 in complex with other nucleoporins and RanGTP.…”

Section: Analysis Of Pbp1 Functionsmentioning

confidence: 99%

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An Integrative Approach to Gain Insights into the Cellular Function of Human Ataxin-2

Ralser

Albrecht

Nonhoff

et al. 2005

Journal of Molecular Biology

135

145

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Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder caused by a trinucleotide expansion in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2 (ATX2), whose cellular function is unknown. However, ATX2 interacts with A2BP1, a protein containing an RNA-recognition motif, and the existence of an interaction motif for the C-terminal domain of the poly(A)-binding protein (PABC) as well as an Lsm (Like Sm) domain in ATX2 suggest that ATX2 like its yeast homolog Pbp1 might be involved in RNA metabolism. Here, we show that, similar to Pbp1, ATX2 suppresses the petite (pet K ) phenotype of Dmrs2 yeast strains lacking mitochondrial group II introns. This finding points to a close functional relationship between the two homologs. To gain insight into potential functions of ATX2, we also generated a comprehensive protein interaction network for Pbp1 from publicly available databases, which implicates Pbp1 in diverse RNA-processing pathways. The functional relationship of ATX2 and Pbp1 is further corroborated by the experimental confirmation of the predicted interaction of ATX2 with the cytoplasmic poly(A)-binding protein 1 (PABP) using yeast-2-hybrid analysis as well as co-immunoprecipitation experiments. Immunofluorescence studies revealed that ATX2 and PABP co-localize in mammalian cells, remarkably, even under conditions in which PABP accumulates in distinct cytoplasmic foci representing sites of mRNA triage.

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Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Pbp1 Functionsmentioning

confidence: 99%

An Integrative Approach to Gain Insights into the Cellular Function of Human Ataxin-2

Ralser

Albrecht

Nonhoff

et al. 2005

Journal of Molecular Biology

135

145

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“…Interestingly, DDX6 is a homologue of yeast Dhh1, which interacts with the Ccr4 -Not complex (Coller et al, 2001;Maillet and Collart, 2002). Moreover, like CNOT7 and CNOT8, DDX6 is a component of cytoplasmic P-bodies (Cougot et al, 2004), which are enriched in translationally repressed mRNA molecules and proteins participating in microRNA-mediated translational repression and mRNA decay (Garneau et al, 2007;Parker and Sheth, 2007).…”

Section: Cnot7 and Cnot8 Are Important For Efficient Cell Proliferatimentioning

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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“…Physical and genetic interactions was amplified by PCR from a HeLa cell cDNA expression library and cloned into a derivative of a yeast expression vector between Dhh1p and Ccr4p, Pop2p, and Not1p have (pG1;Schena et al 1991) containing two HA epitope sebeen reported (Hata et al 1998;Coller et al 2001; quences inserted at the BamHI site. CLN3 derivatives were Maillet and Collart 2002). Ccr4p is the catalytic subexpressed from the GAL1 promoter using the vector pYES2 unit in the yeast deadenylation machinery, and Pop2p (Clontech, Palo Alto, CA).…”

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confidence: 99%

An Essential Role for the Saccharomyces cerevisiae DEAD-Box Helicase DHH1 in G1/S DNA-Damage Checkpoint Recovery

Bergkessel¹,

Reese

2004

Genetics

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The eukaryotic cell cycle displays a degree of plasticity in its regulation; cell cycle progression can be transiently arrested in response to environmental stresses. While the signaling pathways leading to cell cycle arrest are beginning to be well understood, the regulation of the release from arrest has not been well characterized. Here we show that DHH1, encoding a DEAD-box RNA helicase orthologous to the human putative proto-oncogene p54/RCK, is important in release from DNA-damage-induced cell cycle arrest at the G1/S checkpoint. DHH1 mutants are not defective for DNA repair and recover normally from the G2/M and replication checkpoints, suggesting a specific function for Dhh1p in recovery from G1/S checkpoint arrest. Dhh1p has been suggested to play a role in partitioning mRNAs between translatable and nontranslatable pools, and our results implicate this modulation of mRNA metabolism in the recovery from G1/S cell cycle arrest following DNA damage. Furthermore, the high degree of conservation between DHH1 and its human ortholog suggests that this mechanism is conserved among all eukaryotes and potentially important in human disease.

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Interaction between Not1p, a Component of the Ccr4-Not Complex, a Global Regulator of Transcription, and Dhh1p, a Putative RNA Helicase

Cited by 91 publications

References 25 publications

An Integrative Approach to Gain Insights into the Cellular Function of Human Ataxin-2

An Integrative Approach to Gain Insights into the Cellular Function of Human Ataxin-2

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

An Essential Role for the Saccharomyces cerevisiae DEAD-Box Helicase DHH1 in G1/S DNA-Damage Checkpoint Recovery

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