WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies

Mahmoudi, Salah; Henriksson, Sofia; Weibrecht, Irene; Smith, Stephen A.; Söderberg, Ola; Strömblad, Staffan; Wiman, Klas G.; Farnebo, Marianne

doi:10.1371/journal.pbio.1000521

Cited by 120 publications

(189 citation statements)

References 35 publications

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“…39,[44][45][46][47] WRAP53 interacts with coilin, providing the mechanistic link between telomerase and coilin. 48,49 Telomerase RNA localization to CBs was suggested to be important for telomerase function and mislocalization of telomerase RNA from CBs correlates with reduced telomerase activity. 45,50,51 In addition, coilin depletion by siRNA inhibits association of telomerase with telomeres.…”

Section: Coilin Historymentioning

confidence: 99%

Coilin: The first 25 years

2015

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Section: Coilin Historymentioning

confidence: 99%

Coilin: The first 25 years

2015

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“…90 Similarly, depletion of other factors involved in small RNP biogenesis, such as Tgs1, WDR79/WRAP53, PHAX, INTS4 and USPL1 also cause Cajal bodies to disassemble. [91][92][93][94][95] In addition to overall protein levels, post-translational modifications (PTMs) of resident proteins, including SMN and coilin, are almost certainly important for establishing and maintaining inter-and intra-molecular interactions within Cajal bodies. [96][97][98][99][100] Disruption of these PTMs can result in mislocalization of SMN and alterations in Cajal body integrity.…”

Section: Inter-and Intra-molecular Interactions Within the Cajal Bodymentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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“…At least 17 variants of this gene were identified, generated through alternative splicing as well as three different transcription start sites. So far, the reported function of the WRAP53 protein is without obvious relation to p53 (Mahmoudi et al, 2010), but it has been reported that exon 1a of the WRAP53 mRNA contributes to the induction of p53 in response to DNA damage. In Figure 5a, the 10 transcripts listed in the Ensembl database were aligned with the TP53 gene.…”

Section: Chemotherapeutic Drugs Differentially Induce Mutant P53 Levelsmentioning

confidence: 99%

Anthracyclines induce the accumulation of mutant p53 through E2F1-dependent and -independent mechanisms

Bug

Dobbelstein

2011

Oncogene

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Mutant p53 frequently accumulates in cancer cells and promotes tumor cell invasion, as part of its gain of function. Its accumulation is partially due to enhanced stability, but little is known about how the mRNA levels of mutant p53 can be regulated. Likewise, the impact of cancer therapy on the levels of mutant p53 is poorly understood. We show here that the anthracyclines doxorubicin, daunorubicin and epirubicin further increase the amounts of mutant p53 mRNA and protein in cancer cells. Moreover, we show for the first time that the transcription factor E2F1 associates with the promoter DNA of TP53. Upon genotoxic treatment, E2F1 contributed to the expression of mutant p53, both directly and through induction of TAp73. In contrast, the anthracycline idarubicin and also another topoisomerase inhibitor, etoposide, failed to increase the levels of p53 mRNA, despite their ability to induce the synthesis of TAp73 mRNA. Instead, a natural antisense transcript of TP53, WRAP53, was strongly augmented by idarubicin and etoposide, but only less so by the other anthracyclines under study. RNA corresponding to the first exon of WRAP53 was mainly found in cell nuclei and it reduced the levels of mutant p53. Taken together, this suggests a reciprocal activation pattern of TP53 and WRAP53 by different chemotherapeutics. Reducing the levels of mutant p53 by small-interfering RNA increased chemosensitivity, and idarubicin prevented cell survival more efficiently than the mutant p53-inducing doxorubicin. We conclude that even closely related anthracyclines induce the synthesis of different, opposing transcripts from the TP53 locus. When using these drugs for cancer therapy, the increased levels of mutant p53 may augment its gain of function and thus favor unwanted chemoresistance and tumor progression.

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WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies

Abstract: The WRAP53 protein regulates the formation and maintenance of Cajal bodies (nuclear sub-organelles), as well as directs the recruitment of nuclear factors to Cajal bodies.

Cited by 120 publications

References 35 publications

Coilin: The first 25 years

Coilin: The first 25 years

SMN - A chaperone for nuclear RNP social occasions?

Anthracyclines induce the accumulation of mutant p53 through E2F1-dependent and -independent mechanisms

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