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Cholino-ncRNAs modulate sex-specific- and age-related acetylcholine signals.

ABSTRACT: Acetylcholine (ACh) signaling orchestrates mammalian movement, mental capacities, and inflammation. Dysregulated ACh signaling associates with many human mental disorders and neurodegeneration in an individual-, sex-, and tissue-related manner. Moreover, aged patients under anticholinergic therapy show increased risk of dementia, but the underlying molecular mechanisms are incompletely understood. Here, we report that certain cholinergic-targeting noncoding RNAs, named Cholino-noncoding RNAs (ncRNAs), can modulate ACh signaling, agonistically or antagonistically, via distinct direct and indirect mechanisms and at different timescales. Cholino-ncRNAs include both small microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). The former may attenuate translation and/or induce destruction of target mRNAs that code for either ACh-signaling proteins or transcription factors controlling the expression of cholinergic genes. lncRNAs may block miRNAs via 'sponging' events or by competitive binding to the cholinergic target mRNAs. Also, single nucleotide polymorphisms in either Cholino-ncRNAs or in their recognition sites in the ACh-signaling associated genes may modify ACh signaling-regulated processes. Taken together, both inherited and acquired changes in the function of Cholino-ncRNAs impact ACh-related deficiencies, opening new venues for individual, sex-related, and age-specific oriented research, diagnosis, and therapeutics.

SUBMITTER: Madrer N

PROVIDER: S-EPMC7496432 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Cholino-ncRNAs modulate sex-specific- and age-related acetylcholine signals.

Madrer Nimrod N Soreq Hermona H

FEBS letters 20200504 14

Acetylcholine (ACh) signaling orchestrates mammalian movement, mental capacities, and inflammation. Dysregulated ACh signaling associates with many human mental disorders and neurodegeneration in an individual-, sex-, and tissue-related manner. Moreover, aged patients under anticholinergic therapy show increased risk of dementia, but the underlying molecular mechanisms are incompletely understood. Here, we report that certain cholinergic-targeting noncoding RNAs, named Cholino-noncoding RNAs (nc ...[more]

PMID: 32330292

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Project description:BackgroundMany echinoderms form seasonal aggregations prior to spawning. In some fecund species, a spawning event can lead to population outbreaks with detrimental ecosystem impacts. For instance, outbreaks of crown-of-thorns starfish (COTS), a corallivore, can destroy coral reefs. Here, we examine the gene expression in gravid male and female COTS prior to spawning in the wild, to identify genome-encoded factors that may regulate aggregation and spawning. This study is informed by a previously identified exoproteome that attracts conspecifics. To capture the natural gene expression profiles, we isolated RNAs from gravid female and male COTS immediately after they were removed from the Great Barrier Reef. RESULTS: Sexually dimorphic gene expression is present in all seven somatic tissues and organs that we surveyed and in the gonads. Approximately 40% of the exoproteome transcripts are differentially expressed between sexes. Males uniquely upregulate an additional 68 secreted factors in their testes. A suite of neuropeptides in sensory organs, coelomocytes and gonads is differentially expressed between sexes, including the relaxin-like gonad-stimulating peptide and gonadotropin-releasing hormones. Female sensory tentacles-chemosensory organs at the distal tips of the starfish arms-uniquely upregulate diverse receptors and signalling molecules, including chemosensory G-protein-coupled receptors and several neuropeptides, including kisspeptin, SALMFamide and orexin.ConclusionsAnalysis of 103 tissue/organ transcriptomes from 13 wild COTS has revealed genes that are consistently differentially expressed between gravid females and males and that all tissues surveyed are sexually dimorphic at the molecular level. This finding is consistent with female and male COTS using sex-specific pheromones to regulate reproductive aggregations and synchronised spawning events. These pheromones appear to be received primarily by the sensory tentacles, which express a range of receptors and signalling molecules in a sex-specific manner. Furthermore, coelomocytes and gonads differentially express signalling and regulatory factors that control gametogenesis and spawning in other echinoderms.

Dataset Information

Cholino-ncRNAs modulate sex-specific- and age-related acetylcholine signals.

Publications

Cholino-ncRNAs modulate sex-specific- and age-related acetylcholine signals.

Similar Datasets

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