Coordinate regulation of mRNA decay networks by GU-rich elements and CELF1

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

doi:10.1016/j.gde.2011.03.002

Cited by 62 publications

(30 citation statements)

References 70 publications

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“…The decay of ARE-containing mRNAs begins with either synchronous or distributive poly(A) shortening 42 , with the subsequent steps targeting the body of the mRNA from both ends (Box 1, panel A) via the actions of the 5′-3′ and 3′-5′ exonucleases 43 . There are other cis-acting instability elements, the best studied of which are the GU-rich elements (GREs) 44 . GREs function in post-transcriptional regulons involving pre-mRNA splicing and mRNA decay that are coordinated by binding of the CUG-BP Elav-like family (CELF) proteins, the best known of which is CELF1 (also called CUG-BP1) 45,46 .…”

Section: Are-mediated Mrna Decaymentioning

confidence: 99%

Regulation of cytoplasmic mRNA decay

2012

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Discoveries made over the past 20 years highlight the importance of mRNA decay as a means to modulate gene expression and thereby protein production. Up until recently, studies focused largely on identifying cis-acting sequences that serve as mRNA stability or instability elements, the proteins that bind these elements, how the process of translation influences mRNA decay, and the ribonucleases that catalyze decay. Now, current studies have begun to elucidate how the decay process is regulated. This review examines our current understanding of how mammalian-cell mRNA decay is controlled by different signaling pathways and lays out a framework for future research.

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Section: Are-mediated Mrna Decaymentioning

confidence: 99%

Regulation of cytoplasmic mRNA decay

2012

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“…For example, the HuR protein influences decay or translation of numerous mRNA targets involved in cell proliferation, survival, evasion of immune recognition, metastasis and angiogenesis 19 . Like HuR, CELF1 and its target mRNAs are involved in post-transcriptional regulatory networks that control cell growth, activation and differentiation 20 . Because of this, inappropriate expression of a single RBP can impact a wide-range of cellular functions in a coordinated fashion to profoundly change the phenotype of the cell.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of RNA-binding protein CELF1 prevents apoptosis and destabilizes pro-apoptotic mRNAs in oral cancer cells

et al. 2013

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CELF1 RNA-binding protein, otherwise called CUGBP1, associates and coordinates the degradation of GU-rich element (GRE) containing mRNA’s encoding factors important for cell growth, migration and apoptosis. Although many substrates of CELF1 have been identified, the biological significance of CELF1-mediated mRNA decay remains unclear. As the processes modulated by CELF1 are frequently disrupted in cancer, we investigated the expression and role of CELF1 in oral squamous cancer cells (OSCCs). We determined that CELF1 is reproducibly overexpressed in OSCC tissues and cell lines. Moreover, depletion of CELF1 reduced proliferation and increased apoptosis in OSCCs, but had negligible effect in non-transformed cells. We found that CELF1 associates directly with the 3′UTR of mRNAs encoding the pro-apoptotic factors BAD, BAX and JunD and mediates their rapid decay. Specifically, 3′UTR fragment analysis of JunD revealed that the GRE region is critical for binding with CELF1 and expression of JunD in oral cancer cells. In addition, silencing of CELF1 rendered BAD, BAX and JunD mRNAs stable and increased their protein expression in oral cancer cells. Taken together, these results support a critical role for CELF1 in modulating apoptosis and implicate this RNA-binding protein as a cancer marker and potential therapeutic target.

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“…The inhibition of CUGBP1 in HeLa cells stabilizes these mRNAs, while the insertion of the GREs from these transcripts into the stable β-globin mRNA reduces stability of β-globin mRNA (Vlasova et al, 2008). Analysis of CUGBP1 associated transcripts in HeLa cells has been performed by this group and has shown that CUGBP1 binds to hundreds of transcripts containing the GRE element (Rattenbacher et al, 2010; Vlasova-St Luis et al, 2011). Because CUGBP1 contains three RNA Binding Domains (RBD, see figure 1), further studies have examined the binding specificity of these domains and showed that the first two RBDs of CUGBP1 interact with GRE and CUG repeats (Edwards et al, 2011; Teplova et al, 2010).…”

Section: A Multi-functional Cug Triplet Repeat Binding Protein Cumentioning

confidence: 99%