Identification of cis-acting elements involved in Acetylcholinesterase RNA alternative splicing

Guerra, Matt; Dobbertin, Alexandre; Legay, Claire

doi:10.1016/j.mcn.2008.01.007

Cited by 9 publications

(12 citation statements)

References 55 publications

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“…We found that blocks E5a-Δ4d, E5a-Δ5b and E5a-Δ5c potentially harbor splicing regulatory cis -elements. A previously identified branch point sequence (BPS) in rat Ache (14) is mapped to E5a-Δ5b in human ACHE . The putative BPSs in E5a-Δ5b in human ACHE were at 304 to 317 nucleotides upstream to the distal 3΄ ss (green letters in Supplementary Figure S5A).…”

Section: Resultsmentioning

confidence: 99%

“…previously identified that the branch point for the distal 3΄ ss is located 278 nucleotides upstream to the distal 3΄ ss in rat Ache (14). We have shown that human ACHE carries six redundant branch point A nucleotides at 304–317 nucleotides upstream to the distal 3΄ ss (Supplementary Figure S5).…”

Section: Discussionmentioning

confidence: 97%

“…Guerra et al. previously identified the branch point and the polypyrimidine tract, as well as four splicing regulatory cis -elements comprised of 5 to 9 nucleotides, in exon 5a in the rat Ache gene (Figure 2A, B and Supplementary Figure S2A), although an RNA binding-protein for each cis -element was not determined (14). Ubiquitously expressed splicing factors, SRSF1 (SF2/ASF) and SRSF2 (SC-35), were reported to up- and down-regulate the relative expression ratio of human AChE T to AChE R transcripts, respectively (15).…”

Section: Introductionmentioning

confidence: 98%

“…Asterisks indicate that the reverse primer for detecting AChE R and AChE H are different from the others, because the primer-binding site is deleted in these constructs. Previously identified regulatory cis -elements (AB1, B3, E1, E2 and the branch point (BP)) (14) in rat Ache are aligned to human ACHE , and are indicated below the schemes. Note that BP is more conserved than the other 4 elements (see Supplementary Figure S2A).…”

Section: Introductionmentioning

confidence: 99%

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Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

et al. 2016

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Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3΄ end generates three distinct isoforms of AChET, AChEH and AChER. We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3΄ splice site (ss) between exons 5a and 5b to generate AChET. Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site (PAS), which additionally ensures transcription of the distal 3΄ ss required for the generation of AChET. Expression levels of hnRNP H were positively correlated with the proportions of the AChET isoform in three different cell lines. HnRNP H thus critically generates AChET by enhancing the distal 3΄ ss and by suppressing the cryptic PAS. Global analysis of CLIP-seq and RNA-seq also revealed that hnRNP H competitively regulates alternative 3΄ ss and alternative PAS in other genes. We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

et al. 2016

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“…However, some discordance between SC35 protein and AChE R mRNA levels in developing and post-stress cortex were apparent (Meshorer et al, 2005), indicating that other trans-acting factors may also govern splicing of precursor AChE mRNAs. In agreement with this view, Guerra et al used an AChE minigene and sequence mutagenesis to uncover various putative motifs, predominantly located in the E5 non-coding region, that influence production of the R/H/T splice variants in skeletal muscle cells (Guerra et al, 2008). …”

Section: Regulation Of Ache Pre-mrna Splicingmentioning

confidence: 96%

Trans-acting factors governing acetylcholinesterase mRNA metabolism in neurons

Bronicki¹,

Jasmin²

2012

Front. Mol. Neurosci.

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The most characterized function of acetylcholinesterase (AChE) is to terminate cholinergic signaling at neuron-neuron and neuro-muscular synapses. In addition, AChE is causally or casually implicated in neuronal development, stress-response, cognition, and neurodegenerative diseases. Given the importance of AChE, many studies have focused on identifying the molecular mechanisms that govern its expression. Despite these efforts, post-transcriptional control of AChE mRNA expression is still relatively unclear. Here, we review the trans-acting factors and cis-acting elements that are known to control AChE pre-mRNA splicing, mature mRNA stability and translation. Moreover, since the Hu/ELAV family of RNA-binding proteins (RBPs) have emerged in recent years as “master” post-transcriptional regulators, we discuss the possibility that predominantly neuronal ELAVs (nELAVs) play multiple roles in regulating splicing, stability, localization, and translation of AChE mRNA.

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Characterization of the rat Acetylcholinesterase readthrough (AChE-R) splice variant: Implications for toxicological studies

Padhi

Pelletier

Singh

et al. 2020

Biochemical and Biophysical Research Communications

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Identification of cis-acting elements involved in Acetylcholinesterase RNA alternative splicing

Cited by 9 publications

References 55 publications

Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

Trans-acting factors governing acetylcholinesterase mRNA metabolism in neurons

Characterization of the rat Acetylcholinesterase readthrough (AChE-R) splice variant: Implications for toxicological studies

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