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The importance of CELF control: molecular and biological roles of the CUG‐BP, Elav‐like family of RNA‐binding proteins

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Abstract RNA processing is important for generating protein diversity and modulating levels of protein expression. The CUG‐BP, Elav‐like family (CELF) of RNA‐binding proteins regulate several steps of RNA processing in the nucleus and cytoplasm, including pre‐mRNA alternative splicing, C to U RNA editing, deadenylation, mRNA decay, and translation. In vivo, CELF proteins have been shown to play roles in gametogenesis and early embryonic development, heart and skeletal muscle function, and neurosynaptic transmission. Dysregulation of CELF‐mediated programs has been implicated in the pathogenesis of human diseases affecting the heart, skeletal muscles, and nervous system. WIREs RNA 2012, 3:104–121. doi: 10.1002/wrna.107 This article is categorized under: Translation > Translation Regulation RNA Processing > Splicing Regulation/Alternative Splicing RNA Turnover and Surveillance > Regulation of RNA Stability Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

All six human CUG‐BP, Elav‐like family (CELF) proteins share a common domain structure, with three RNA recognition motif (RRM) RNA‐binding domains and a divergent domain between the second and third RRM.8 Each family member exists in multiple isoforms because of alternative splicing and/or the generation of alternative 5′ ends by differential promoter usage (not shown).

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CUG‐BP, Elav‐like family (CELF) proteins regulate translation through multiple mechanisms. (a) The Drosophila CELF protein, Bru, forms a complex with Cup and the 5′ cap binding initiation factor, eIF4E, leading to circularization and translational repression of the mRNA. (b) CELF2 inhibits translation by binding to A/U‐rich elements in the 3′ UTR and competing with HuR, an activator of translation. (c) Binding of CELF1 to sequences in the short open reading frame (sORF) in the 5′ region of C/EPBβ promotes usage of a downstream start codon, giving rise to the truncated liver inhibitory protein (LIP) protein. Phosphorylated CELF1 interacts with the initiation factor, eIF2, which is thought to promote use of the downstream AUG by increased ribosome scanning. (d) Interaction of CELF1 and hnRNP H at the two ends of the transcript aids circularization. This has been proposed to facilitate translation from an internal ribosome entry site (IRES) by increasing ribosome recycling.

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RNA Turnover and Surveillance > Regulation of RNA Stability
RNA Processing > Splicing Regulation/Alternative Splicing
Translation > Translation Regulation
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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