RNA binding protein RALY promotes Protein Arginine Methyltransferase 1 alternatively spliced isoform v2 relative expression and metastatic potential in breast cancer cells

Bondy‐Chorney, Emma; Baldwin, R. Mitchell; Didillon, Andréanne; Chabot, Benoît; Jasmin, Bernard J.; Côté, Jocelyn

doi:10.1016/j.biocel.2017.07.008

Cited by 25 publications

(21 citation statements)

References 67 publications

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“…Interestingly, PRMT1 mRNA is a direct target of RALY and RALY knockdown determines a significant decrease in PRMT1v2 mRNA and protein inside the cell, consequently determining a reduction of invasiveness. The overexpression of PRMT1v2 in RALY-down-regulated cells rescues the aggressive phenotype of the breast cancer cells (76). These results demonstrate the direct involvement of RALY in the splicing of a specific mRNA with consequent effects on cell phenotype.…”

Section: Raly Regulates E2f1 Stabilitymentioning

confidence: 59%

“…RALY could be involved in the 3Ј-end processing of coding as well as noncoding RNAs, ultimately affecting RNA stability, but further experiments are needed to better elucidate this possibility. Recently, RALY was described as having a direct role in regulating the splicing of the protein arginine methyltransferase 1 (PRMT1) mRNA, coding for a factor involved in the post-translational methylation of proteins and found to be aberrantly regulated in different cancers (76). A spliced isoform of PRMT1 that includes the alternative second exon (PRMT1v2) was found to be up-regulated in breast cancer and was correlated with high aggressiveness (77).…”

Section: Raly Regulates E2f1 Stabilitymentioning

confidence: 99%

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The hnRNP RALY regulates transcription and cell proliferation by modulating the expression of specific factors including the proliferation marker E2F1

Cornella

Tebaldi

Gasperini

et al. 2017

Journal of Biological Chemistry

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The heterogeneous nuclear ribonucleoproteins (hnRNP) form a large family of RNA-binding proteins that exert numerous functions in RNA metabolism. RALY is a member of the hnRNP family that binds poly-U-rich elements within several RNAs and regulates the expression of specific transcripts. RALY is up-regulated in different types of cancer, and its down-regulation impairs cell cycle progression. However, the RALY's role in regulating RNA levels remains elusive. Here, we show that numerous genes coding for factors involved in transcription and cell cycle regulation exhibit an altered expression in RALY-down-regulated HeLa cells, consequently causing impairments in transcription, cell proliferation, and cell cycle progression. Interestingly, by comparing the list of RALY targets with the list of genes affected by RALY down-regulation, we found an enrichment of RALY mRNA targets in the down-regulated genes upon RALY silencing. The affected genes include the E2F transcription factor family. Given its role as proliferation-promoting transcription factor, we focused on E2F1. We demonstrate that mRNA stability and E2F1 protein levels are reduced in cells lacking RALY expression. Finally, we also show that RALY interacts with transcriptionally active chromatin in both an RNA-dependent and -independent manner and that this association is abolished in the absence of active transcription. Taken together, our results highlight the importance of RALY as an indirect regulator of transcription and cell cycle progression through the regulation of specific mRNA targets, thus strengthening the possibility of a direct gene expression regulation exerted by RALY.

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Section: Raly Regulates E2f1 Stabilitymentioning

confidence: 59%

Section: Raly Regulates E2f1 Stabilitymentioning

confidence: 99%

The hnRNP RALY regulates transcription and cell proliferation by modulating the expression of specific factors including the proliferation marker E2F1

Cornella

Tebaldi

Gasperini

et al. 2017

Journal of Biological Chemistry

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“…AMBRA1 is a regulator of autophagy and has been shown to affect drug resistance in several cancers [115][116][117]. RALY is an RNA-binding protein implicated in metastasis and associated with poor prognosis in breast and colorectal cancer and hepatocellular carcinoma [118][119][120]. More analysis to identify novel fusion transcripts at the RNA level could identify more novel, poorly understood drivers that have been missed through traditional analysis but may have meaningful implications.…”

Section: Identification Of Rare Eventsmentioning

confidence: 99%

Transposon Insertion Mutagenesis in Mice for Modeling Human Cancers: Critical Insights Gained and New Opportunities

Beckmann

Largaespada

2020

IJMS

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Transposon mutagenesis has been used to model many types of human cancer in mice, leading to the discovery of novel cancer genes and insights into the mechanism of tumorigenesis. For this review, we identified over twenty types of human cancer that have been modeled in the mouse using Sleeping Beauty and piggyBac transposon insertion mutagenesis. We examine several specific biological insights that have been gained and describe opportunities for continued research. Specifically, we review studies with a focus on understanding metastasis, therapy resistance, and tumor cell of origin. Additionally, we propose further uses of transposon-based models to identify rarely mutated driver genes across many cancers, understand additional mechanisms of drug resistance and metastasis, and define personalized therapies for cancer patients with obesity as a comorbidity.

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“…The expression of alternatively spliced PRMT1 (PRMT1v2) isoform, which is generated through inclusion of alternative exon 2, is significantly altered in breast cancer and promotes invasiveness. The RNA binding protein RALY regulates the PRMT1v2 isoform and promotes metastatic potential [109].…”

Section: Arginine Methylationmentioning

confidence: 99%

The Landscape of Histone Modification in Cancer Metastasis

Qiu¹,

Wang²,

Wu³

2018

Cancer Metastasis

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Metastasis represents one of the most devastating aspects of cancer. Epithelial to mesenchymal transition (EMT) has been shown to play a critical role in tumorigenic metastasis. During metastatic progression, both genetic and epigenetic modifications endow cancer cells with properties that modulate the capacity for metastatic success. Histone modification is profoundly altered in cancer cells and contributes to cancer metastasis by controlling different metastatic phenotypes. Here, we first review histone modifications and discuss their roles in EMT and metastasis, with a particular focus on histone methylation and acetylation. Second, we review the major histone modification enzymes that control chromatin in cancer metastasis. Third, we discuss the transcriptional regulation concerted by these enzymes with EMT transcription factors at different molecular layers. Finally, we discuss pharmacologic manipulation of histone modification enzymes for metastasis treatment. A comprehensive understanding of histone modification in metastasis will not only provide new insights into our knowledge of cancer progression and metastasis, but also offer a novel approach for the development of innovative therapeutic strategies.

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RNA binding protein RALY promotes Protein Arginine Methyltransferase 1 alternatively spliced isoform v2 relative expression and metastatic potential in breast cancer cells

Cited by 25 publications

References 67 publications

The hnRNP RALY regulates transcription and cell proliferation by modulating the expression of specific factors including the proliferation marker E2F1

The hnRNP RALY regulates transcription and cell proliferation by modulating the expression of specific factors including the proliferation marker E2F1

Transposon Insertion Mutagenesis in Mice for Modeling Human Cancers: Critical Insights Gained and New Opportunities

The Landscape of Histone Modification in Cancer Metastasis

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