Global assessment of GU-rich regulatory content and function in the human transcriptome

Halees, Anason S.; Hitti, Edward; Al-Saif, Maher; Mahmoud, Linah; Louis, Irina Vlasova-St.; Beisang, Daniel; Bohjanen, Paul R.; Khabar, Khalid S.A.

doi:10.4161/rna.8.4.16283

Cited by 39 publications

(35 citation statements)

References 33 publications

(41 reference statements)

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“…92 GREs exist in arrangements of 2 to 5 overlapping pentamers, however in contrast to AREs, mRNA decay effectiveness does not seem to depend on the number of repetitions. 91 Also, functional similarity to ARE is observed in GREs. GREs are present in the 3' UTR of short-lived mRNAs in T-lymphocytes, where they cause a rapid mRNA decay.…”

Section: Waf1mentioning

confidence: 99%

“…At least 5% of human mRNAs contain a GU-rich element (GRE) in their 3' UTR. 91 GRE resembles the ARE by the character of the basic sequence pentamer motif ("GUUUG"), while the minimal functional length of the element was identified to be an 11 base (sequence "UGU UUG UUU GU"). 92 GREs exist in arrangements of 2 to 5 overlapping pentamers, however in contrast to AREs, mRNA decay effectiveness does not seem to depend on the number of repetitions.…”

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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“…The top two consensus sequences within this group of transcripts resembled the GRE. These results suggest that CELF1 in malignant T cells interacts with target transcripts through GRE sequences that are similar to known CELF1 target sequences in normal T cells and other cell types (Halees et al 2011). …”

Section: Celf1 Targets In Malignant T-cell Lines Exhibited Acceleratementioning

confidence: 88%

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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“…Adenylate uridylate-rich elements (AREs) are the most common and best characterized of these cis-acting elements identified to date and may be present in approximately 10% of all human transcripts (2,14). Guanidylate-uridylaterich elements (GREs) represent another class of cis-acting determinants of deadenylation-dependent mRNA decay (58). Although these elements target mRNAs for degradation, they are subject to complex regulation by a variety of RBPs under different physiological conditions (49).…”

Section: Role Of Mrna Stability In the Regulation Of Gene Expressionmentioning

confidence: 99%

Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

McKay

2014

Antioxidants & Redox Signaling

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Significance: Production of proteins requires the synthesis, maturation, and export of mRNAs before their translation in the cytoplasm. Endogenous and exogenous sources of DNA damage pose a challenge to the coordinated regulation of gene expression, because the integrity of the DNA template can be compromised by DNA lesions. Cells recognize and respond to this DNA damage through a variety of DNA damage responses (DDRs). Failure to deal with DNA damage appropriately can lead to genomic instability and cancer. Recent Advances: The p53 tumor suppressor plays a dominant role in DDR-dependent changes in gene expression, but this transcription factor is not solely responsible for all changes. Recent evidence indicates that RNA metabolism is integral to DDRs as well. In particular, post-transcriptional processes are emerging as important contributors to these complex responses. Critical Issues: Transcriptional, post-transcriptional, and translational regulation of gene expression is subject to changes in response to DNA damage. How these processes are intertwined in the unfolding of DDR is not fully understood. Future Directions: Many complex regulatory responses combine to determine cell fate after DNA damage. Understanding how transcriptional, post-transcriptional, and translational processes interdigitate to create a web of regulatory interactions will be one of the key challenges to fully understand DDRs. Antioxid. Redox Signal. 20, 640-654.

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Global assessment of GU-rich regulatory content and function in the human transcriptome

Cited by 39 publications

References 33 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.

Altered CELF1 binding to target transcripts in malignant T cells

Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

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