Translational control by cytoplasmic polyadenylation in Xenopus oocytes

Radford, Helois; Meijer, Hedda A.; Moor, Cornelia H. de

doi:10.1016/j.bbagrm.2008.02.002

Cited by 178 publications

(204 citation statements)

References 153 publications

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“…There are eight candidate poly(A) polymerase genes in the human genome: PAPa-g (PAPOLA,B,G), PAPD1, PAPD2, PAPD4, PAPD5, and PAPD7 (Hirose and Manley 1998;Wahle and Rüegsegger 1999;Topalian et al 2001;Houseley and Tollervey 2008;Kashiwabara et al 2008;Radford et al 2008;Rammelt et al 2011). They have a variety of substrates and functions, ranging from targeting aberrant transcripts for degradation in the nucleus to stabilizing microRNAs in the cytoplasm (Katoh et al 2009;Shcherbik et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of polyadenylation reduces inflammatory gene induction

Kondrashov

Meijer

Barthet-Barateig

et al. 2012

RNA

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Cordycepin (39 deoxyadenosine) has long been used in the study of in vitro assembled polyadenylation complexes, because it terminates the poly(A) tail and arrests the cleavage complex. It is derived from caterpillar fungi, which are highly prized in Chinese traditional medicine. Here we show that cordycepin specifically inhibits the induction of inflammatory mRNAs by cytokines in human airway smooth muscle cells without affecting the expression of control mRNAs. Cordycepin treatment results in shorter poly(A) tails, and a reduction in the efficiency of mRNA cleavage and transcription termination is observed, indicating that the effects of cordycepin on 39 processing in cells are similar to those described in in vitro reactions. For the CCL2 and CXCL1 mRNAs, the effects of cordycepin are post-transcriptional, with the mRNA disappearing during or immediately after nuclear export. In contrast, although the recruitment of RNA polymerase II to the IL8 promoter is also unaffected, the levels of nascent transcript are reduced, indicating a defect in transcription elongation. We show that a reporter construct with 39 sequences from a histone gene is unaffected by cordycepin, while CXCL1 sequences confer cordycepin sensitivity to the reporter, demonstrating that polyadenylation is indeed required for the effect of cordycepin on gene expression. In addition, treatment with another polyadenyation inhibitor and knockdown of poly(A) polymerase a also specifically reduced the induction of inflammatory mRNAs. These data demonstrate that there are differences in the 39 processing of inflammatory and housekeeping genes and identify polyadenylation as a novel target for anti-inflammatory drugs.

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Section: Discussionmentioning

confidence: 99%

Inhibition of polyadenylation reduces inflammatory gene induction

Kondrashov

Meijer

Barthet-Barateig

et al. 2012

RNA

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“…c-Mos and cyclin B1) that have been reported to be newly synthesized during maturation are translated only after complex phosphorylation and processing events occurring at the 3Ј-untranslated region of the mRNA (67). These events involve Maskin and the cytoplasmic element-binding protein, two known substrates of Aurora A (42,68), and require the presence of a cytoplasmic polyadenylation element in the 3Ј-untranslated region of the target mRNA (67). Since examination of the p53 gene revealed the presence of a cytoplasmic polyadenylation element motif in its 3Ј-untranslated region, it seems likely that p53 translation may be regulated by Aurora A during maturation.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of p53 Is Regulated by TPX2-Aurora A in Xenopus Oocytes

Pascreau

Eckerdt

Lewellyn

et al. 2009

Journal of Biological Chemistry

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p53 is an important tumor suppressor regulating the cell cycle at multiple stages in higher vertebrates. The p53 gene is frequently deleted or mutated in human cancers, resulting in loss of p53 activity. This leads to centrosome amplification, aneuploidy, and tumorigenesis, three phenotypes also observed after overexpression of the oncogenic kinase Aurora A. Accordingly, recent studies have focused on the relationship between these two proteins. p53 and Aurora A have been reported to interact in mammalian cells, but the function of this interaction remains unclear. We recently reported that Xenopus p53 can inhibit Aurora A activity in vitro but only in the absence of TPX2. Here we investigate the interplay between Xenopus Aurora A, TPX2, and p53 and show that newly synthesized TPX2 is required for nearly all Aurora A activation and for full p53 synthesis and phosphorylation in vivo during oocyte maturation. In vitro, phosphorylation mediated by Aurora A targets serines 129 and 190 within the DNA binding domain of p53. Glutathione S-transferase pull-down studies indicate that the interaction occurs via the p53 transactivation domain and the Aurora A catalytic domain around the T-loop. Our studies suggest that targeting of TPX2 might be an effective strategy for specifically inhibiting the phosphorylation of Aurora A substrates, including p53.

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“…plu 6 and gnu 305 are described in refs. 11 and 44. mr 1 and mr 2 are female-sterile alleles (27,45). The UASp gnu-GFP transgenic line was obtained from Myles Axton (29).…”

Section: Methodsmentioning

confidence: 99%

“…It is driven by Maturation Promoting Factor (MPF), the Cyclin B/CDK1 kinase complex. The regulation of the meiotic cell cycle at maturation is best understood in Xenopus, where control of translation by polyadenylation leads to the translation of both Cyclin B to produce MPF and the Mos kinase, which is crucial in maintaining the secondary meiotic arrest (1). In Drosophila oogenesis, some mRNAs become polyadenylated at maturation, dependent on the GLD2 cytoplasmic poly(A) polymerase (2).…”

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confidence: 99%