Posttranscriptional regulation of gene networks by GU-rich elements and CELF proteins

Vlasova, Irina A.; Bohjanen, Paul R.

doi:10.4161/rna.7056

Cited by 75 publications

(87 citation statements)

References 95 publications

(121 reference statements)

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“…As they are highly conserved through animal species, they are considered to constitute an evolutionary conserved pathway for regulation of post-transcriptional events such as pre-mRNA splicing, mRNA deadenylation and degradation. 93 Although two members of this family-human proteins CUGBP1 and CUGBP2-are almost identical in their RNA-binding domains, they play different roles in posttranscriptional regulation. While CUGBP1 has destabilizing effects on mRNA followed by increased translation efficiency, CUGBP2 shows exactly the opposite effects of stabilizing mRNA and inhibiting translation.…”

Section: Waf1mentioning

confidence: 99%

“…92 In association with binding proteins, GREs contribute to regulation of post-transcriptional events such as deadenylation, mRNA decay and pre-mRNA splicing. 93 Recently, proteins from the CELF family (CUGBP and embryonically lethal abnormal vision-type RNA-binding protein 3-like factors) were identified together with the recognition of GU-rich elements. As they are highly conserved through animal species, they are considered to constitute an evolutionary conserved pathway for regulation of post-transcriptional events such as pre-mRNA splicing, mRNA deadenylation and degradation.…”

Section: Waf1mentioning

confidence: 99%

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The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells.

et al. 2012

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Section: Waf1mentioning

confidence: 99%

Section: Waf1mentioning

confidence: 99%

The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells.

et al. 2012

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“…CELF1 was subsequently identified as a protein that specifically bound to the GRE in vitro and then to regulate the decay of exogenously expressed GRE-containing transcripts within cells [30], [141]. Further verification of the role of CELF1 in GRE-mediated mRNA decay came from the observation that in HeLa cells, siRNA-mediated knockdown of CELF1 led to stabilization of GRE-containing beta-globin reporter transcripts, as well as endogenous GRE-containing transcripts [30], [83], [142].…”

Section: Mrna Decaymentioning

confidence: 99%

CELF1, a Multifunctional Regulator of Posttranscriptional Networks

Beisang¹,

Bohjanen²,

Louis³

2012

Binding Protein

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“…A more recently identified regulatory motif, known as the GU-rich element (GRE), is found in the 3 ′ untranslated regions (UTRs) of transcripts that encode regulators of cell growth, activation, differentiation, and apoptosis Beisang and Bohjanen 2012). The GRE serves as the binding target of the protein, CUGBP and ELAV-like family member 1 (CELF1), which functions to mediate the rapid degradation of GREcontaining transcripts (Vlasova and Bohjanen 2008). During T-cell activation, GREs coordinate the degradation of transcripts involved in cell growth and apoptosis (Beisang et al 2012b).…”

Section: Introductionmentioning

confidence: 99%

Altered CELF1 binding to target transcripts in malignant T cells

Bohjanen

Moua

Guo

et al. 2015

RNA

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The RNA-binding protein, CELF1, binds to a regulatory sequence known as the GU-rich element (GRE) and controls a network of mRNA transcripts that regulate cellular activation, proliferation, and apoptosis. We performed immunoprecipitation using an anti-CELF1 antibody, followed by identification of copurified transcripts using microarrays. We found that CELF1 is bound to a distinct set of target transcripts in the H9 and Jurkat malignant T-cell lines, compared with primary human T cells. CELF1 was not phosphorylated in resting normal T cells, but in malignant T cells, phosphorylation of CELF1 correlated with its inability to bind to GRE-containing mRNAs that served as CELF1 targets in normal T cells. Lack of binding by CELF1 to these mRNAs in malignant T cells correlated with stabilization and increased expression of these transcripts. Several of these GRE-containing transcripts that encode regulators of cell growth were also stabilized and up-regulated in primary tumor cells from patients with T-cell acute lymphoblastic leukemia. Interestingly, transcripts encoding numerous suppressors of cell proliferation that served as targets of CELF1 in malignant T cells, but not normal T cells, exhibited accelerated degradation and reduced expression in malignant compared with normal T cells, consistent with the known function of CELF1 to mediate degradation of bound transcripts. Overall, CELF1 dysfunction in malignant T cells led to the up-regulation of a subset of GRE-containing transcripts that promote cell growth and down-regulation of another subset that suppress cell growth, producing a net effect that would drive a malignant phenotype.

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Posttranscriptional regulation of gene networks by GU-rich elements and CELF proteins

Cited by 75 publications

References 95 publications

The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells.

The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells.

CELF1, a Multifunctional Regulator of Posttranscriptional Networks

Altered CELF1 binding to target transcripts in malignant T cells

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