CELF1, a Multifunctional Regulator of Posttranscriptional Networks

Beisang, Daniel; Bohjanen, Paul R.; Louis, Irina Vlasova-St.

doi:10.5772/48780

Cited by 9 publications

(7 citation statements)

References 165 publications

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“…A well-utilized rabbit beta-globin reporter system identified GREs as sequences that regulate the decay of exogenously expressed GRE-containing reporter transcripts within cells [13]. Further verification of GRE-mediated mRNA decay came from the observation that siRNA-mediated knockdown of protein CELF1 led to the stabilization of GRE-containing beta-globin reporter transcripts as well as endogenous GRE-containing transcripts [49][50][51]. These studies also showed that both GU-rich sequences and GU repeats are also enriched in unstable mRNAs, though a number of GUUUG pentamers in the GRE do not seem to correlate with the mRNA decay rate.…”

Section: Gu-rich Element (Gre)mentioning

confidence: 99%

Mammalian Cis-Acting RNA Sequence Elements

Louis¹,

Sagarsky²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects

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Cis-acting regulatory sequence elements are sequences contained in the 3 0 and 5 0 untranslated region, introns, or coding regions of precursor RNAs and mature mRNAs that are selectively recognized by a complementary set of one or more trans-acting factors to regulate posttranscriptional gene expression. This chapter focuses on mammalian cis-acting regulatory elements that had been recently discovered in different regions: pre-processed and mature. The chapter begins with an overview of two large networks of mRNAs that contain conserved AU-rich elements (AREs) or GU-rich elements (GREs), and their role in mammalian cell physiology. Other, less conserved, cisacting elements and their functional role in different steps of RNA maturation and metabolism will be discussed. The molecular characteristics of pathological cis-acting sequences that rose from gene mutations or transcriptional aberrations are briefly outlined, with the proposed approach to restore normal gene expression. Concise models of the function of posttranscriptional regulatory networks within different cellular compartments conclude this chapter.

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Section: Gu-rich Element (Gre)mentioning

confidence: 99%

Mammalian Cis-Acting RNA Sequence Elements

Louis¹,

Sagarsky²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects

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“…This leads to transient stabilization and upregulation of GRE-containing transcripts, including components of cytokine and growth factor signaling [7, 130] [133]. Thus, CELF1 functions in normal cells to down-regulate the expression of GRE-containing transcripts that promote cell growth, including multiple components of cytokine and growth factor signaling pathways [134]. …”

Section: Regulation Of Cytokine and Growth Factor Network By Gresmentioning

confidence: 99%

Post-transcriptional regulation of cytokine and growth factor signaling in cancer

Louis

Bohjanen

2017

Cytokine & Growth Factor Reviews

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Cytokines and growth factors regulate cell proliferation, differentiation, migration and apoptosis, and play important roles in coordinating growth signal responses during development. The expression of cytokine genes and the signals transmitted through cytokine receptors are tightly regulated at several levels, including transcriptional and post-transcriptional levels. A majority of cytokine mRNAs, including growth factor transcripts, contain AU-rich elements (AREs) in their 3’ untranslated regions that control gene expression by regulating mRNA degradation and changing translational rates. In addition, numerous proteins involved in transmitting signals downstream of cytokine receptors are regulated at the level of mRNA degradation by GU-rich elements (GREs) found in their 3’ untranslated regions. Abnormal stabilization and overexpression of ARE or GRE-containing transcripts had been observed in many malignancies, which is a consequence of the malfunction of RNA-binding proteins. In this review, we briefly summarize the role of AREs and GREs in regulating mRNA turnover to coordinate cytokine and growth factor expression, and we describe how dysregulation of mRNA degradation mechanisms contributes to the development and progression of cancer.

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“…CELF1 is an RNA-BP that regulates a network of transcripts that control important cellular functions such as cell growth and apoptosis by binding to GREs in the 3’UTR of target transcripts [ 55 ]. Along with ELAVL1, discussed below, CELF1 is a prototypic member of a family of RNA-binding proteins known as the CUGBP1 and ELAV-like family (CELF) of proteins ( Figure 1 ) [ 27 ].…”

Section: Regulation Of Celf1 Function By Phosphorylationmentioning

confidence: 99%

Feedback Regulation of Kinase Signaling Pathways by AREs and GREs

Louis

Bohjanen

2016

Cells

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In response to environmental signals, kinases phosphorylate numerous proteins, including RNA-binding proteins such as the AU-rich element (ARE) binding proteins, and the GU-rich element (GRE) binding proteins. Posttranslational modifications of these proteins lead to a significant changes in the abundance of target mRNAs, and affect gene expression during cellular activation, proliferation, and stress responses. In this review, we summarize the effect of phosphorylation on the function of ARE-binding proteins ZFP36 and ELAVL1 and the GRE-binding protein CELF1. The networks of target mRNAs that these proteins bind and regulate include transcripts encoding kinases and kinase signaling pathways (KSP) components. Thus, kinase signaling pathways are involved in feedback regulation, whereby kinases regulate RNA-binding proteins that subsequently regulate mRNA stability of ARE- or GRE-containing transcripts that encode components of KSP.

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CELF1, a Multifunctional Regulator of Posttranscriptional Networks

Cited by 9 publications

References 165 publications

Mammalian Cis-Acting RNA Sequence Elements

Mammalian Cis-Acting RNA Sequence Elements

Post-transcriptional regulation of cytokine and growth factor signaling in cancer

Feedback Regulation of Kinase Signaling Pathways by AREs and GREs

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