Intron Retention as a Posttranscriptional Regulatory Mechanism of Neurotoxin Expression at Early Life Stages of the Starlet Anemone Nematostella vectensis

Moran, Yehu; Weinberger, Hagar; Reitzel, Adam M.; Sullivan, James C.; Kahn, Roy; Gordon, Dalia; Finnerty, John R.; Gurevitz, Michael

doi:10.1016/j.jmb.2008.05.011

Cited by 43 publications

(44 citation statements)

References 34 publications

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“…This pattern is indicative of strong positive selection for amino acid replacements because it implies that the rate of non-synonymous changes exceeds that which can be explained solely by a neutral substitution rate. These emerging features reflect the evolutionary mechanisms described previously for some toxins affecting voltage-gated sodium channels from sea anemones [2,3], isozymes of snake venom [22,23], and toxins from scorpions [24], which have evolved in an adaptive manner under positive Darwinian selection (“accelerated evolution”). Hence, selection promotes the fixation of non-synonymous substitutions and accelerates the diversification of related sequences.…”

Section: Resultssupporting

confidence: 68%

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Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis

et al. 2013

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Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our cDNA libraries. The calculation of the relative abundance of BDS transcripts in the cDNA libraries revealed that BDS-1, BDS-3, BDS-4, BDS-5 and BDS-6 are the most represented transcripts.

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Section: Resultssupporting

confidence: 68%

“…The sea anemone Anemonia viridis is a widespread and extensively studied Mediterranean species [2,3,4,5,6], from which a large number of polypeptide toxins, including sodium and potassium ion channel modulators or blockers, as well as Kunitz-type protease inhibitors, have been isolated [7]. …”

Section: Introductionmentioning

confidence: 99%

Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis

et al. 2013

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“…50%) to Nv1 [14]. Nevertheless, the structure of Av2, the most abundant A. viridis neurotoxin, resembles that of Nv1 [19] and the anti-Nv1 antibody recognizes recombinant Av2 in ELISA (electronic supplementary material, figure S1). …”

Section: Resultsmentioning

confidence: 99%

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

et al. 2011

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Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

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“…Among these three splicing events, intron retention is the least studied; it is primarily thought to be a consequence of inefficient splicing since retained introns can affect mRNA transport and stability. However, intron rention is quite prevalent in plants (Ner-Gaon et al, 2004) and unicellular organisms, and can act as a post-transcriptional regulatory mechanism (Boothby et al, 2013; Moran et al, 2008). Recent genomic studies suggest intron retention may also be prevalent in mammals (Mauger et al, 2016; Wong et al, 2016) and may contribute to the generation of specific protein variants (Altieri, 1994; Bell et al, 2010; Ebihara et al, 1996), cell-type specific expression (Wong et al, 2013; Yap et al, 2012), fine-tuned gene expression (Braunschweig et al, 2014), and mRNA targetting (Buckley et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Regulated Intron Removal Integrates Motivational State and Experience

Gill

Park

McGinnis

et al. 2017

Cell

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Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen indentified pasilla, the fly orthologue of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.

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Intron Retention as a Posttranscriptional Regulatory Mechanism of Neurotoxin Expression at Early Life Stages of the Starlet Anemone Nematostella vectensis

Cited by 43 publications

References 34 publications

Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis

Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

Regulated Intron Removal Integrates Motivational State and Experience

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