ArticleMolecular and cellular biology2007
Human TOB, an antiproliferative transcription factor, is a poly(A)-binding protein-dependent positive regulator of cytoplasmic mRNA deadenylation.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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99 citing papers in PubMed, 165 citations in OpenAlex.
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- Concerted action of ataxin-2 and PABPC1-bound mRNA poly(A) tail in the formation of stress granules.Nucleic acids research · 2024Article
- Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD.Non-coding RNA · 2024Review
- TOB1 and TOB2 mark distinct RNA processing granules in differentiating lens fiber cells.Journal of molecular histology · 2024Article
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- Non-Coding RNAs and Gut Microbiota in the Pathogenesis of Cardiac Arrhythmias: The Latest Update.Genes · 2023Review
- RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent deadenylation of the nanos mRNA in a reconstituted system.Nucleic acids research · 2023Article
- CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders.Non-coding RNA · 2023Review
- Article
- Structure and function of molecular machines involved in deadenylation-dependent 5'-3' mRNA degradation.Frontiers in genetics · 2023Review
- Regulation of eukaryotic mRNA deadenylation and degradation by the Ccr4-Not complex.Frontiers in cell and developmental biology · 2023Review
- Regulation of the multisubunit CCR4-NOT deadenylase in the initiation of mRNA degradation.Current opinion in structural biology · 2022Review
- Control of immediate early gene expression by CPEB4-repressor complex-mediated mRNA degradation.Genome biology · 2022Article
- Cnot8 eliminates naïve regulation networks and is essential for naïve-to-formative pluripotency transition.Nucleic acids research · 2022Article
- BTG2 suppresses renal cell carcinoma progression through N6-methyladenosine.Frontiers in oncology · 2022Article
- RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation.Nature communications · 2021Article
- A conserved motif in human BTG1 and BTG2 proteins mediates interaction with the poly(A) binding protein PABPC1 to stimulate mRNA deadenylation.RNA biology · 2021Article
- Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex.Nucleic acids research · 2021Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
In mammalian cells, mRNA decay begins with deadenylation, which involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. The regulation of the critical deadenylation step and its relationship with RNA-processing bodies (P-bodies), which are thought to be a site where poly(A)-shortened mRNAs get degraded, are poorly understood. Using the Tet-Off transcriptional pulsing approach to investigate mRNA decay in mouse NIH 3T3 fibroblasts, we found that TOB, an antiproliferative transcription factor, enhances mRNA deadenylation in vivo. Results from glutathione S-transferase pull-down and coimmunoprecipitation experiments indicate that TOB can simultaneously interact with the poly(A) nuclease complex CCR4-CAF1 and the cytoplasmic poly(A)-binding protein, PABPC1. Combining these findings with those from mutagenesis studies, we further identified the protein motifs on TOB and PABPC1 that are necessary for their interaction and found that interaction with PABPC1 is necessary for TOB's deadenylation-enhancing effect. Moreover, our immunofluorescence microscopy results revealed that TOB colocalizes with P-bodies, suggesting a role of TOB in linking deadenylation to the P-bodies. Our findings reveal a new mechanism by which the fate of mammalian mRNA is modulated at the deadenylation step by a protein that recruits poly(A) nuclease(s) to the 3' poly(A) tail-PABP complex.
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