Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs

Weidensdorfer, D; Stöhr, Nadine; Baude, Anne; Lederer, Marcell; Köhn, Marcel; Schierhorn, Angelika; Buchmeier, Sabine; Wahle, Elmar; Hüttelmaier, Stefan

doi:10.1261/rna.1175909

Cited by 276 publications

(314 citation statements)

References 22 publications

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…Similar to Ro, YB-1 accumulates in nuclei after UV irradiation (Koike et al 1997). Consistent with a related function, Ro, YB-1, and nucleolin all copurify with human ZBP1 (Jonson et al 2007;Weidensdorfer et al 2009), a protein that functions in mRNA localization, translational regulation, and mRNA stability (Ross et al 1997;Doyle et al 1998;Nielsen et al 1999;Hüttelmaier et al 2005). MOV10, which associates with microRNAs as part of RISC (Meister et al 2005), has been found with Ro, La, YB-1, and nucleolin in purifications of APOBEC3G, a cytidine deaminase involved in protecting the human genome from retroviruses and endogenous retrotransposons (Chiu et al 2006;Kozak et al 2006;Gallois-Montbrun et al 2007).…”

Section: Identification Of Ro-associated Proteinssupporting

confidence: 66%

The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA

Sim¹,

Yao²,

Weinberg³

et al. 2011

RNA

View full text Add to dashboard Cite

The Ro 60-kDa autoantigen, a ring-shaped RNA-binding protein, traffics between the nucleus and cytoplasm in vertebrate cells. In some vertebrate nuclei, Ro binds misfolded noncoding RNAs and may function in quality control. In the cytoplasm, Ro binds noncoding RNAs called Y RNAs. Y RNA binding blocks a nuclear accumulation signal, retaining Ro in the cytoplasm. Following UV irradiation, this signal becomes accessible, allowing Ro to accumulate in nuclei. To investigate how other cellular components influence the function and subcellular location of Ro, we identified several proteins that copurify with the mouse Ro protein. Here, we report that the zipcode-binding protein ZBP1 influences the subcellular localization of both Ro and the Y3 RNA. Binding of ZBP1 to the Ro/Y3 complex increases after UV irradiation and requires the Y3 RNA. Despite the lack of an identifiable CRM1-dependent export signal, nuclear export of Ro is sensitive to the CRM1 inhibitor leptomycin B. In agreement with a previous report, we find that ZBP1 export is partly dependent on CRM1. Both Ro and Y3 RNA accumulate in nuclei when ZBP1 is depleted. Our data indicate that ZBP1 may function as an adapter to export the Ro/Y3 RNA complex from nuclei.

show abstract

Section: Identification Of Ro-associated Proteinssupporting

confidence: 66%

The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA

Sim¹,

Yao²,

Weinberg³

et al. 2011

RNA

View full text Add to dashboard Cite

show abstract

“…Transcriptional machinery across TCF7L2 key SNP Q Xia et al 5 0 direction and thereby regulate the interactions between proteins and DNA or RNA; 36 indeed, RNA helicases participate in multiple biological processes, including transcription, splicing and translation. 37 The mechanism by which these three protein operate resonates with the fact that the open chromatin in islets has been reported to differ between alleles of this key SNP.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the transcriptional machinery bound across the widely presumed type 2 diabetes causal variant, rs7903146, within TCF7L2

et al. 2014

View full text Add to dashboard Cite

Resolving the underlying functional mechanism to a given genetic association has proven extremely challenging. However, the strongest associated type 2 diabetes (T2D) locus reported to date, TCF7L2, presents an opportunity for translational analyses, as many studies in multiple ethnicities strongly point to SNP rs7903146 in intron 3 as being the causal variant within this gene. We carried out oligo pull-down combined with mass spectrophotometry (MS) to elucidate the specific transcriptional machinery across this SNP using protein extracts from HCT116 cells. We observed that poly (ADP-ribose) polymerase 1 (PARP-1) is by far the most abundant binding factor. Pursuing the possibility of a feedback mechanism, we observed that PARP-1, along with the next most abundant binding proteins, DNA topoisomerase I and ATP-dependent RNA helicase A, dimerize with the TCF7L2 protein and with each other. We uncovered further evidence of a feedback mechanism using a luciferase reporter approach, including observing expression differences between alleles for rs7903146. We also found that there was an allelic difference in the MS results for proteins with less abundant binding, namely X-ray repair cross-complementing 5 and RPA/p70. Our results point to a protein complex binding across rs7903146 within TCF7L2 and suggests a possible mechanism by which this locus confers its T2D risk.

show abstract

“…IGF2BP1 targets c-myc mRNA, preventing degradation of the mRNA signal and constitutively activating its expression. 16,30 IGF2BP1 also inhibits MAPK4 mRNA translation. 27 This enhances tumor cell migration by reducing downstream sequestration of G-actin, which facilitates the turnover of actin in the cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Methylation markers of malignant potential in meningiomas

Vengoechea

Sloan

Chen³

et al. 2013

JNS

View full text Add to dashboard Cite

Object Although most meningiomas are benign, about 20% are atypical (Grade II or III) and have increased mortality and morbidity. Identifying tumors with greater malignant potential can have significant clinical value. This validated genome-wide methylation study comparing Grade I with Grade II and III meningiomas aims to discover genes that are aberrantly methylated in atypical meningiomas. Methods Patients with newly diagnosed meningioma were identified as part of the Ohio Brain Tumor Study. The Infinium HumanMethylation27 BeadChip (Illumina, Inc.) was used to interrogate 27,578 CpG sites in 14,000 genes per sample for a discovery set of 33 samples (3 atypical). To verify the results, the Infinium HumanMethylation450 BeadChip (Illumina, Inc.) was used to interrogate 450,000 cytosines at CpG loci throughout the genome for a verification set containing 7 replicates (3 atypical), as well as 12 independent samples (6 atypical). A nonparametric Wilcoxon exact test was used to test for difference in methylation between benign and atypical meningiomas in both sets. Heat maps were generated for each set. Methylation results were validated for the 2 probes with the largest difference in methylation intensity by performing Western blot analysis on a set of 20 (10 atypical) samples, including 11 replicates. Results The discovery array identified 95 probes with differential methylation between benign and atypical meningiomas, creating 2 distinguishable groups corresponding to tumor grade when visually examined on a heat map. The validation array evaluated 87 different probes and showed that 9 probes were differentially methylated. On heat map examination the results of this array also suggested the existence of 2 major groups that corresponded to histological grade. IGF2BP1 and PDCD1, 2 proteins that can increase the malignant potential of tumors, were the 2 probes with the largest difference in intensity, and for both of these the atypical meningiomas had a decreased median production of protein, though this was not statistically significant (p = 0.970 for IGF2BP1 and p = 1 for PDCD1). Conclusions A genome-wide methylation analysis of benign and atypical meningiomas identified 9 genes that were reliably differentially methylated, with the strongest difference in IGF2BP1 and PDCD1. The mechanism why increased methylation of these sites is associated with an aggressive phenotype is not evident. Future research may investigate this mechanism, as well as the utility of IGF2BP1 as a marker for pathogenicity in otherwise benign-appearing meningiomas.

show abstract

Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs

Cited by 276 publications

References 22 publications

The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA

The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA

Characterization of the transcriptional machinery bound across the widely presumed type 2 diabetes causal variant, rs7903146, within TCF7L2

Methylation markers of malignant potential in meningiomas

Contact Info

Product

Resources

About