ELAV mediates 3′ UTR extension in the <i>Drosophila</i> nervous system

Hilgers, Valérie; Lemke, Sandra B.; Levine, Michael

doi:10.1101/gad.199653.112

Cited by 102 publications

(127 citation statements)

References 36 publications

(40 reference statements)

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“…For example, tissue-specific knockdown of Elav in the wing pouch did not overtly affect wing development (data not shown). Nevertheless, Elav is a powerful and multifaceted post-transcriptional regulator that orchestrates alternative splicing, 3′ end formation and alternative polyadenylation (Hilgers et al, 2012;Koushika et al, 2000;Lisbin et al, 2001;Soller and White, 2003), and it would not be surprising for basal Elav to have demonstrable effects. Indeed, we visualized that ectopic Elav generated in miRNA pathway mutant clones upregulates a transgenic Elav sensor.…”

Section: Discussionmentioning

confidence: 99%

Neural specificity of the RNA-binding protein Elav is achieved by post-transcriptional repression in non-neural tissues

et al. 2016

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Drosophila Elav is the founding member of the conserved family of Hu RNA-binding proteins (RBPs), which play crucial and diverse roles in post-transcriptional regulation. Elav has long served as the canonical neuronal marker. Surprisingly, although Elav has a well-characterized neural cis-regulatory module, we find endogenous Elav is also ubiquitously transcribed and post-transcriptionally repressed in non-neural settings. Mutant clones of multiple miRNA pathway components derepress ubiquitous Elav protein. Our re-annotation of the elav transcription unit shows not only that it generates extended 3′ UTR isoforms, but also that its universal 3′ UTR isoform is much longer than previously believed. This longer common 3′ UTR includes multiple conserved, high-affinity sites for the miR-279/996 family. Of several miRNA mutants tested, endogenous Elav and a transgenic elav 3′ UTR sensor are derepressed in mutant clones of mir-279/996. We also observe cross-repression of Elav by Mei-P26, another RBP derepressed in non-neural miRNA pathway clones. Ubiquitous Elav has regulatory capacity, since derepressed Elav can stabilize an Elavresponsive sensor. Repression of Elav in non-neural territories is crucial as misexpression here has profoundly adverse consequences. Altogether, we define unexpected post-transcriptional mechanisms that direct appropriate cell type-specific expression of a conserved neural RBP.

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Section: Discussionmentioning

confidence: 99%

Neural specificity of the RNA-binding protein Elav is achieved by post-transcriptional repression in non-neural tissues

et al. 2016

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“…Since the 6.0-kb variant is less stable and not as efficiently translated as the 2.4-kb transcript, the authors postulated that the reduction of HuR expression prevents HuR's ability to promote proliferation and thereby permits neurons to terminally differentiate (Mansfield and Keene 2011). The role of Hu proteins in controlling alternative polyadenylation is likely extended to several of their target mRNAs, given that the ELAV protein in Drosophila was found to coordinate 3 ′ UTR extension of multiple mRNAs in neuronal cells (Hilgers et al 2012).…”

Section: Alternative Polyadenylationmentioning

confidence: 99%

Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction

Bronicki

Jasmin

2013

RNA

107

118

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Precise control of messenger RNA (mRNA) processing and abundance are increasingly being recognized as critical for proper spatiotemporal gene expression, particularly in neurons. These regulatory events are governed by a large number of transacting factors found in neurons, most notably RNA-binding proteins (RBPs) and micro-RNAs (miRs), which bind to specific cisacting elements or structures within mRNAs. Through this binding mechanism, trans-acting factors, particularly RBPs, control all aspects of mRNA metabolism, ranging from altering the transcription rate to mediating mRNA degradation. In this context the best-characterized neuronal RBP, the Hu/ELAVl family member HuD, is emerging as a key component in multiple regulatory processes-including pre-mRNA processing, mRNA stability, and translation-governing the fate of a substantial amount of neuronal mRNAs. Through its ability to regulate mRNA metabolism of diverse groups of functionally similar genes, HuD plays important roles in neuronal development and function. Furthermore, compelling evidence indicates supplementary roles for HuD in neuronal plasticity, in particular, recovery from axonal injury, learning and memory, and multiple neurological diseases. The purpose of this review is to provide a detailed overview of the current knowledge surrounding the expression and roles of HuD in the nervous system. Additionally, we outline the present understanding of the molecular mechanisms presiding over the localization, abundance, and function of HuD in neurons.

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“…Similarly, the cytoplasmic polyadenylation element-binding protein 1 (CPEB1) binds upstream of the weaker proximal poly(A) signal and recruits the CPSF complex to promote 3′-UTR shortening events (Bava et al 2013). By contrast, Drosophila ELAV (embryonic lethal abnormal vision) mediates neural-specific 3′-UTR lengthening by inhibiting proximal APA, which leads to transcriptional read-through and formation of a longer isoform (Hilgers et al 2012).…”

Section: Role Of Rbps In Apa Decisionsmentioning

confidence: 99%

Alternative polyadenylation and RNA-binding proteins

Erson-Bensan

2016

Journal of Molecular Endocrinology

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Our understanding of the extent of microRNA-based gene regulation has expanded in an impressive pace over the past decade. Now, we are beginning to better appreciate the role of 3′-UTR (untranslated region) cis-elements which harbor not only microRNA but also RNA-binding protein (RBP) binding sites that have significant effect on the stability and translational rate of mRNAs. To add further complexity, alternative polyadenylation (APA) emerges as a widespread mechanism to regulate gene expression by producing shorter or longer mRNA isoforms that differ in the length of their 3′-UTRs or even coding sequences. Resulting shorter mRNA isoforms generally lack cis-elements where trans-acting factors bind, and hence are differentially regulated compared with the longer isoforms. This review focuses on the RBPs involved in APA regulation and their action mechanisms on APA-generated isoforms. A better understanding of the complex interactions between APA and RBPs is promising for mechanistic and clinical implications including biomarker discovery and new therapeutic approaches.

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ELAV mediates 3′ UTR extension in the Drosophila nervous system

Cited by 102 publications

References 36 publications

Neural specificity of the RNA-binding protein Elav is achieved by post-transcriptional repression in non-neural tissues

Neural specificity of the RNA-binding protein Elav is achieved by post-transcriptional repression in non-neural tissues

Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction

Alternative polyadenylation and RNA-binding proteins

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