Post‐transcriptional regulation in cancer

Audic, Yann; Hartley, Rebecca S.

doi:10.1016/j.biolcel.2004.05.002

Cited by 206 publications

(207 citation statements)

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“…60 These results are consistent with data demonstrating that inhibition of expression of the Wig-1 ortholog PAG608 using antisense RNA led to attenuated p53-dependent methamphetamineinduced cell death. 20 Most ARE-BPs regulate multiple mRNAs 54,56 , and our preliminary results indicate that Wig-1 also can target other ARE-containing mRNAs apart from p53. 60 …”

Section: Wig-1 Functionmentioning

confidence: 73%

“…The AREs are elements involved in regulation mRNA stability and translation, and consist of the element AUUUA in various constellations or of exclusively U-rich regions. 53,54 They are present in 5-8 % of the transcriptome, mostly in mRNAs of genes whose expression is precisely controlled, including genes encoding proteins that regulate cell growth or the cellular response to external factors, for example, c-Myc, N-Myc, cyclins, interferons, p53 and p21. 53,54 AREs are generally considered as negative regulators of gene expression.…”

Section: Wig-1 Functionmentioning

confidence: 99%

“…53,54 They are present in 5-8 % of the transcriptome, mostly in mRNAs of genes whose expression is precisely controlled, including genes encoding proteins that regulate cell growth or the cellular response to external factors, for example, c-Myc, N-Myc, cyclins, interferons, p53 and p21. 53,54 AREs are generally considered as negative regulators of gene expression. They can mediate mRNA degradation both by increasing deadenylation, which is the first and rate-limiting step of mRNA degradation, and by enhancing subsequent decay of the mRNA.…”

Section: Wig-1 Functionmentioning

confidence: 99%

“…53,55 Wig-1 regulates mRNA stability and stem cell fate A Vilborg et al ARE-binding proteins (ARE-BPs) are important nodes of regulation, as they can potentially control the levels of many different mRNAs in the cell. 54,56 The 3 0 UTR of p53 harbors one U-rich region (18 continuous Us) and one additional ARE, 57,58 both of which are targeted for regulation by several ARE-BPs. 59 Wig-1 binds to the U-rich region in the 3 0 UTR of p53 mRNA and stabilizes p53 mRNA by preventing its deadenylation (Figure 2b).…”

Section: Wig-1 Functionmentioning

confidence: 99%

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The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

et al. 2011

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Wig-1 is a transcriptional target of the tumor suppressor p53 and encodes an unusual zinc-finger protein involved in posttranscriptional gene regulation. Wig-1 is expressed in all cell types investigated so far, with the highest levels in the brain, and is enriched in stem cells as compared with more differentiated cells of the same lineage. Wig-1 binds to both long double-stranded (ds) RNA and short microRNA-like dsRNA. We have shown that Wig-1 acts in a positive feedback loop that stabilizes p53 mRNA through an AU-rich element (ARE) in the p53 3 0 untranslated region. Our preliminary data indicate a more general effect of Wig-1 on ARE-containing mRNA. Here we shall summarize current knowledge about Wig-1 and discuss possible implications on p53 function and other cellular processes.

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Section: Wig-1 Functionmentioning

confidence: 73%

Section: Wig-1 Functionmentioning

confidence: 99%

Section: Wig-1 Functionmentioning

confidence: 99%

Section: Wig-1 Functionmentioning

confidence: 99%

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The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

et al. 2011

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“…[2] Given the important function of RBPs in gene expression, it is not surprising that deregulated or mutated RBPs contribute to cancer progression. [3], [4], [5] Dysfunctional or mutated RBPs can cause increased expression of oncogenes or decreased expression of tumor suppressor genes such as the p53 family members. [6], [7] Recent studies demonstrated that RBPs can protect mRNAs by preventing micro(mi)RNA access to the 3'-UTR and thus protecting them from degradation.…”

Section: Introductionmentioning

confidence: 99%

The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation

et al. 2016

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The RNA binding proteins RBM binding motif protein 38 (RBM38) and DEAD END 1 (DND1) selectively stabilize mRNAs by attenuating RNAse activity or protecting them from micro(mi)RNA-mediated cleavage. Furthermore, both proteins can efficiently stabilize the mRNA of the cell cycle inhibitor p21 CIP1 . Since acute myeloid leukemia (AML) differentiation requires cell cycle arrest and RBM38 as well as DND1 have antiproliferative functions, we hypothesized that decreased RBM38 and DND1 expression may contribute to the differentiation block seen in this disease. We first quantified RBM38 and DND1 mRNA expression in clinical AML patient samples and CD34 + progenitor cells and mature granulocytes from healthy donors. We found significantly lower RBM38 and DND1 mRNA levels in AML blasts and CD34 + progenitor cells as compared to mature neutrophils from healthy donors. Furthermore, the lowest expression of both RBM38 and DND1 mRNA correlated with t(8;21). In addition, neutrophil differentiation of CD34 + cells in vitro with G-CSF (granulocyte colony stimulating factor) resulted in a significant increase of RBM38 and DND1 mRNA levels. Similarly, neutrophil differentiation of NB4 acute promyelocytic leukemia (APL) cells was associated with a significant induction of RBM38 and DND1 expression. To address the function of RBM38 and DND1 in neutrophil differentiation, we generated two independent NB4_RBM38 as well as DND1 knockdown cell lines. Inhibition of both RBM38 and DND1 mRNA significantly attenuated NB4 differentiation and resulted in decreased p21 CIP1 mRNA expression. Our results clearly indicate that expression of the RNA binding proteins RBM38 and DND1 is repressed in primary AML patients, that neutrophil differentiation is dependent on increased expression of both proteins, and that these proteins have a critical role in regulating p21 CIP1 expression during APL differentiation. Highlights RBM38 and DND1 expression is attenuated in primary AML patients  Normal and leukemic neutrophil differentiation induces RBM38 and DND1 expression  New function for the RNA binding proteins RBM38 and DND1 in APL differentiation Keywords: RBM38, DND1, acute myeloid leukemia, acute promyelocytic leukemia, neutrophil differentiation

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The 3′ UTR Landscape in Cancer

Schmidt¹,

Ghosh²,

Zavolan³

2018

Encyclopedia of Life Sciences

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Oncogenesis is tightly connected with dysregulated gene expression. Alterations occur at many levels, including in posttranscriptional regulatory elements that control the stability, cellular localisation or translation efficiency of messenger ribonucleic acids (mRNAs). These elements are located primarily in the 3′ untranslated region (UTR) of mRNAs. Multiple examples are known of oncogenes whose activity and function become altered owing to changes in their 3′ UTRs. Strikingly, recent studies have uncovered global changes of 3′ UTRs in cancers, going beyond individual genes. Cancer cells express transcripts with systematically shorter 3′ UTRs compared to normal cells. The implications of these changes for cellular biology are poorly understood, but high‐throughput approaches are being developed to uncover the regulators, targets and impact of 3′ UTR‐based regulation. The hope is that a renewed understanding of 3′ UTR alterations can open new therapeutic opportunities. Key Concepts The maturation of most messenger RNAs includes 3′ end cleavage followed by the addition of a polyadenosine tail. Most human protein‐coding genes express multiple isoforms, which can differ, among others, in their 3′ untranslated regions (3′ UTRs). In proliferating cells, including cancer cells, cleavage and polyadenylation tend to occur at coding region proximal sites, giving rise to isoforms with short 3′ UTRs. As 3′ UTRs contain binding sites for many RNA‐binding regulatory proteins, it is likely that short 3′ UTR isoforms are less susceptible to posttranscriptional regulation. A role of 3′ UTR length changes in the progression and prognosis of cancers has been proposed.

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Post‐transcriptional regulation in cancer

Cited by 206 publications

References 207 publications

The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation

The 3′ UTR Landscape in Cancer

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