H19 RNA Binds Four Molecules of Insulin-like Growth Factor II mRNA-binding Protein

Runge, Steffen; Nielsen, Finn Cilius; Nielsen, Jacob; Lykke-Andersen, Jens; Wewer, Ulla M.; Christiansen, Jan

doi:10.1074/jbc.m001156200

Cited by 148 publications

(127 citation statements)

References 44 publications

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“…Therefore, CRD-BP may regulate cell proliferation in a cell typespecific manner. CRD-BP binds to c-myc, IGF-II, ␤-actin mRNAs, and to H19 RNA, and it affects RNA localization, turnover, and translation (13,19,37,38,46,47). Our results show that among those targets, neither c-myc, ␤-actin, nor H19 RNA appears to be responsible for the proliferative effect of CRD-BP knockdown.…”

Section: Discussionmentioning

confidence: 63%

“…c or con, control siRNA treatment; e or exp, CRD-BP siRNA treatment; n, sample number. the 3Ј terminus of H19 RNA and mediates its subcytoplasmic localization in cultured cells but apparently does not control H19 RNA levels (46). CRD-BP knockdown had no statistical effect on either H19 RNA (p Ͼ 0.05; Fig.…”

Section: Crd-bp Sirna Specifically Inhibits Crd-bp Gene Expression-mentioning

confidence: 99%

“…As controls, the levels of H19 RNA and ␤-actin mRNA were assessed as well. Like IGF-II leader 3 mRNA, H19 RNA and ␤-actin mRNA are binding targets of CRD-BP (46,47). H19 RNA is an untranslated RNA that is imprinted in conjunction with IGF-II (48).…”

Section: Crd-bp Sirna Specifically Inhibits Crd-bp Gene Expression-mentioning

confidence: 99%

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Targeted Knockdown of the RNA-binding Protein CRD-BP Promotes Cell Proliferation via an Insulin-like Growth Factor II-dependent Pathway in Human K562 Leukemia Cells

Liao

Patel

et al. 2004

Journal of Biological Chemistry

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The c-myc mRNA coding region determinant-binding protein (CRD-BP) was first identified as a masking protein that stabilizes c-myc mRNA in a cell-free mRNA degradation system. Thus, CRD-BP is thought to promote cell proliferation by maintaining c-Myc at critical levels. CRD-BP also appears to be an oncofetal protein, based upon its expression during mammalian development and in some tumors. By using K562 leukemia cells as a model, we show that CRD-BP gene silencing by RNA interference significantly promoted proliferation, indicating an inhibitory effect of CRD-BP on proliferation. Unexpectedly, CRD-BP knockdown had no discernible effect on c-myc mRNA levels. CRD-BP is also known as insulin-like growth factor II (IGF-II) mRNA-binding protein-1. It has been reported to repress translation of a luciferase reporter mRNA containing an IGF-II 5 -untranslated region known as leader 3 but not one containing IGF-II leader 4. CRD-BP knockdown markedly increased IGF-II mRNA and protein levels but did not alter translation of luciferase reporter mRNAs containing 5 -untranslated regions consisting of either IGF-II leader 3 or leader 4. Addition of antibody against IGF-II to cell cultures inhibited the proliferative effect of CRD-BP knockdown, suggesting that regulation of IGF-II gene expression, rather than c-myc mRNA levels, mediates the proliferative effect of CRD-BP knockdown. Thus, we have identified a dominant function for CRD-BP in cell proliferation of human K562 cells, involving a possible IGF-II-dependent mechanism that appears independent of its ability to serve as a c-myc mRNA masking protein.

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Section: Discussionmentioning

confidence: 63%

Section: Crd-bp Sirna Specifically Inhibits Crd-bp Gene Expression-mentioning

confidence: 99%

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Targeted Knockdown of the RNA-binding Protein CRD-BP Promotes Cell Proliferation via an Insulin-like Growth Factor II-dependent Pathway in Human K562 Leukemia Cells

Liao

Patel

et al. 2004

Journal of Biological Chemistry

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“…Recently, H19 has been shown to belong to a group of localized untranslated RNA (Runge et al, 2000), we can also speculate that the H19 transcript in¯uences the translatability of Trx mRNA by controlling its subcytoplasmic localization. Finally, the identi®cation of Trx as a target molecule for the H19 gene, moreover positively regulated, allows a better understanding of the function of this riboregulator.…”

mentioning

confidence: 99%

Thioredoxin post-transcriptional regulation by H19 provides a new function to mRNA-like non-coding RNA

et al. 2002

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Classically, the functional product of coding genes is a protein whose synthesis is directed by an mRNAtemplate. However, in the last few years several genes yielding an mRNA-like non-coding RNA as a functional product have been identi®ed. In most cases these transcripts are synthesized by the RNA polymerase II, capped, spliced and polyadenylated, like classical mRNA. These latter have non-conserved open reading frames and seem to be untranslated. Consequently, it has been proposed and admitted that these genes act at the RNA level, and are so-called`riboregulators'. H19 belongs to this class of gene and its role remains a matter of debate: for some authors it is an oncogene, for others a tumour suppressor. Here, we demonstrate, using a proteomic approach, that an H19 overexpression in human cancerous mammary epithelial cells stably transfected with genomic DNA containing the entire H19 gene is responsible for positively regulating at the post-transcriptional level the thioredoxin, a key protein of the cellular redox metabolism. Interestingly, this protein accumulates in many cancerous tissues, such as breast carcinomas in which we have also demonstrated an overexpression of the H19 gene.

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“…Binds to the 3'-UTR of Micropthalmia associated transcription factor mRNA and prevents the binding of miR-340 to its target sites, resulting in stabilization of the transcript, elevated expression and activity of this transcription factor (Goswami et al, 2010). mRNA transportation: IGF2BP1 binds to the fourth and fifth exons of the oncofetal H19 RNA (Runge et al, 2000) and with ELAVL4 and G3BP to 3'-UTR of the neuron-specific TAU mRNA (Atlas et al, 2004;Atlas et al, 2007) and regulates their localization. In collaboration with IGF2BP2, IGF2BP1 binds to the conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA, known as the 'zip code'.…”

Section: Igf2bp1 (Insulin-like Growth Factor 2 Mrna Binding Protein 1)mentioning

confidence: 99%

IGF2BP1 (insulin-like growth factor 2 mRNA binding protein 1)

Trangas¹,

Ioannidis²

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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H19 RNA Binds Four Molecules of Insulin-like Growth Factor II mRNA-binding Protein

Cited by 148 publications

References 44 publications

Targeted Knockdown of the RNA-binding Protein CRD-BP Promotes Cell Proliferation via an Insulin-like Growth Factor II-dependent Pathway in Human K562 Leukemia Cells

Targeted Knockdown of the RNA-binding Protein CRD-BP Promotes Cell Proliferation via an Insulin-like Growth Factor II-dependent Pathway in Human K562 Leukemia Cells

Thioredoxin post-transcriptional regulation by H19 provides a new function to mRNA-like non-coding RNA

IGF2BP1 (insulin-like growth factor 2 mRNA binding protein 1)

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