Two isoforms of the cold‐inducible mRNA‐binding protein RBM3 localize to dendrites and promote translation

Smart, Fiona M.; Aschrafi, Armaz; Atkins, Annette R.; Owens, Geoffrey C.; Pilotte, Julie; Cunningham, Bruce A.; Vanderklish, Peter W.

doi:10.1111/j.1471-4159.2007.04521.x

Cited by 89 publications

(98 citation statements)

References 68 publications

(175 reference statements)

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“…There was a stagedependent increase in RBM3 mRNA levels compared to the paired uninvolved tissues, with the highest levels observed in later stages (Figure 1a). Two novel isoforms, resulting from alternative splicing were recently identified in neurons (Smart et al, 2007). However, these isoforms were not observed in the colon cancer cells (data not shown).…”

Section: Rbm3 Is Induced In Colon Cancersmentioning

confidence: 91%

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

et al. 2008

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RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E 2 , a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.

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Section: Rbm3 Is Induced In Colon Cancersmentioning

confidence: 91%

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

et al. 2008

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“…The observation that RBM3 has a positive effect on protein synthesis suggests that RBM3 may prevent a more dramatic reduction of protein synthesis under conditions of hypothermia (Dresios et al, 2005;Smart et al, 2007). However, it is unlikely that RBM3 rescues neuronal cells from apoptosis by merely stabilizing the translational machinery.…”

Section: Vector-based Rbm3 Over-expression Mimics the Protective Effementioning

confidence: 94%

“…Therefore, it is not surprising that several RNA-binding proteins exhibit a common dynamic expression pattern during postnatal brain development (Hambardzumyan et al, 2009;McKee et al, 2005). Previous reports found RBM3 to be associated with ribosomal subunits (Dresios et al, 2005;Smart et al, 2007) and at least one heterogenous ribonucleoprotein (Sureban et al, 2008).…”

Section: Vector-based Rbm3 Over-expression Mimics the Protective Effementioning

confidence: 99%

“…Then, 24 h after transfection, plates were subjected to the various experiments as indicated. Previously, two RBM3 isoforms have been described differing in one arginine at position 137, encoded by the first three bases of exon 6, isoform Arg+ and Arg- (Smart et al, 2007). Our RBM3-overexpression vector codes for the complete RBM3 protein, including arginine at position 137.…”

Section: Rbm3 Over-expression and Short Interfering Rnamentioning

confidence: 99%

“…Blocking RBM3 signalling by siRNAs triggers cells mitotic catastrophe in colon carcinoma cells (Sureban et al, 2008) and causes loss of proliferation and ultimately cell death in human embryonic kidney cells (HEK-293) (Wellmann et al, 2010). In contrast, exogenous over-expression of RBM3 inhibits apoptosis in neurons transfected with mutated huntingtin (Kita et al, 2002) and increases protein synthesis in mouse neuroblastoma N2a cells (Dresios et al, 2005;Smart et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection

Chip

Zelmer

Ogunshola

et al. 2011

Neurobiology of Disease

115

110

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Induced hypothermia is the only therapy with proven efficacy to reduce brain damage after perinatal asphyxia. While hypothermia down-regulates global protein synthesis and cell metabolism, low temperature induces a small subset of proteins that includes the RNA-binding protein RBM3 (RNA-binding motif protein 3), which has recently been implicated in cell survival. Here, immunohistochemistry of the developing postnatal murine brain revealed a spatio-temporal neuronal RBM3 expression pattern very similar to that of doublecortin, a marker of neuronal precursor cells. Mild hypothermia (32°C) profoundly promoted RBM3 expression and rescued neuronal cells from forced apoptosis as studied in primary neurons, PC12 cells, and cortical organotypic slice cultures. Blocking RBM3 expression in neuronal cells by specific siRNAs significantly diminished the neuroprotective effect of hypothermia while vector-driven RBM3 over-expression reduced cleavage of PARP, prevented internucleosomal DNA fragmentation, and LDH release also in the absence of hypothermia. Together, neuronal RBM3 up-regulation in response to hypothermia apparently accounts for a substantial proportion of hypothermia-induced neuroprotection. Together, neuronal RBM3 up-regulation in response to hypothermia apparently accounts for a substantial proportion of hypothermia-induced neuroprotection.

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RBM3 expression is upregulated by NF‐κB p65 activity, protecting cells from apoptosis, during mild hypothermia

Ushio

Eto²

2018

J of Cellular Biochemistry

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The RNA-binding protein RBM3, a cold shock protein whose expression is elevated under hypothermic conditions, plays an important role in cell survival; however, little is known about the mechanism underlying the mild hypothermia-mediated regulation of RBM3 expression and apoptosis. Here we show that the transcription factor NF-κB p65 is phosphorylated at Ser276 and activates RBM3 gene transcription via binding to a particular element within the promoter region in response to induced hypothermia, elevating the protein expression, and suppressing apoptosis. Treatment with caffeic acid phenethyl ester (CAPE), a potent and specific inhibitor that suppresses the translocation of NF-κB p65 from the cytoplasm to the nucleus, resulted in decreased levels of RBM3 mRNA and protein and increased incidence of apoptosis despite cells were cultured under hypothermic conditions. Overexpression of RBM3 abolished the induction of apoptosis in cells treated with CAPE, indicating that NF-κB p65-upregulated RBM3 expression is necessary for the suppression of apoptosis. In addition, experiments with cells overexpressing RBM3 supported the finding demonstrating that the mild hypothermia-mediated higher expression of RBM3 suppressed the induction of apoptosis. Conversely, experiments with cells deficient in RBM3 supported the finding demonstrating that the CAPE-mediated loss of RBM3 induced apoptosis. These results suggest that NF-κB p65 is a critical mediator of mild hypothermia, to which cells are exposed as an extracellular environment, and a central inducer of RBM3 expression, which is responsible for preventing cells from apoptosis. Moreover, CAPE may have a potential for the application to a therapeutic agent for the treatment of cancers.

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Two isoforms of the cold‐inducible mRNA‐binding protein RBM3 localize to dendrites and promote translation

Cited by 89 publications

References 68 publications

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection

RBM3 expression is upregulated by NF‐κB p65 activity, protecting cells from apoptosis, during mild hypothermia

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