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bioRxiv · 10.1101/831917

Pseudouridine synthases in the RluA family negatively regulate Drosophila nociception.

Song, W.·Tracey, W. D.
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Abstract

Nociceptive neurons of Drosophila melanogaster larvae are characterized by highly branched dendritic processes whose proper morphogenesis relies on a large number of RNA-binding proteins. Post-transcriptional regulation of RNA in these dendrites has been found to play an important role in their function. Here, we investigate the neuronal functions of two putative RNA modification genes, RluA-1 and RluA-2, which are predicted to encode pseudouridine synthases. RluA-1 is specifically expressed in larval sensory neurons while RluA-2 expression is ubiquitous. Nociceptor-specific RNAi knockdown of RluA-1 caused hypersensitive nociception phenotypes, which were recapitulated with genetic null alleles. These were rescued with genomic duplication and nociceptor-specific expression of UAS-RluA-1-cDNA. As with RluA-1, RluA-2 loss of function mutants also displayed hyperalgesia. Interestingly, nociceptor neuron dendrites showed a hyperbranched morphology in the RluA-1 mutants. The latter may be a cause or a consequence of heightened sensitivity in mutant nociception behaviors. Author SummaryPseudouridine (Psi) is a C5-glycoside isomer of uridine and it is the most common posttranscriptional modification of RNAs, including noncoding tRNAs, rRNAs, snRNAs as well as mRNAs. Although first discovered in the 1950s, the biological functions of Psi in multicellular organisms are not well understood. Interestingly, a marker for sensory neurons in Drosophila encodes for a putative pseudouridine synthase called RluA-1. Here, we report our characterization of nociception phenotypes for larvae with RluA-1 loss of function along with that of a related gene RluA-2. Disrupting either or both RluA-1 and RluA-2 resulted in hypersensitive nociception. In addition, RluA-1 mutants have more highly branched nociceptor neurites that innervate the epidermis. Our studies suggest an important role for the RluA family in nociception. This may be through its action on RNAs that regulate neuronal excitability and/or dendrite morphogenesis.

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Song, W., Tracey, W. D.. 2019-11-05. Pseudouridine synthases in the RluA family negatively regulate Drosophila nociception.. https://doi.org/10.1101/831917

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