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Integrated Analysis of MRNA and MiRNA Expression Profiles in dys-1 Mutants of C. Elegans After Spaceflight and Simulated Microgravity

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Abstract

Dystrophin-like dys-1 gene is expressed and required in muscle tissue, playing a vital role in gravisensing in Caenorhabditis elegans (C. elegans). To date, microRNA (miRNA)-mediated epigenetic mechanism in microgravity-induced muscular atrophy remains to be elucidated. In the present study, we first analyzed mRNA and miRNA expression profiles in space-flown dys-1(cx18) mutants and wild type worms (wt) of C. elegans. The results showed that spaceflight and microgravity have fewer effects on mRNA and miRNA expression in dys-1 mutant than in wt worms. mRNA and miRNA expression patterns of dys-1 mutants were changed by microgravity. Hierarchical clustering analysis showed that the alterations of genes function on neuromuscular system under space environment. Seven miRNAs (cel-miR-52, 56, 81, 82, 84, 124 and 230) have 18 significant anti-correlated target genes under space environment. RT-qPCR analysis confirmed that miR-52 and cdh-3, miR-84 and lin-14, miR-124 and mgl-3 in dys-1 mutants reversely altered under microgravity environment and in simulated microgravity experiment. Locomotion ability was only reduced in F0 wt worms but not in dys-1 mutants as well as their F1 offspring after simulated microgravity. We observed expression alterations of 7 neuromuscular genes (unc-27, nlp-22, flp-1, egl-5, flp-4, mgl-3, unc-94) in F0 wt worms, which might be involved in the regulation of locomotion ability of C. elegans. This study provides important insights to reveal the mechanism in the pathogenesis of muscular atrophy induced by microgravity.

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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy of this project.

References

  • Abbott, A.L., Alvarez-Saavedra, E., Miska, E.A., Lau, N.C., Bartel, D.P., Horvitz, H.R., Ambros, V.: The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev. Cell. 9(3), 403–414 (2005)

    Article  Google Scholar 

  • Akima, H., Kawakami, Y., Kubo, K., Sekiguchi, C., Ohshima, H., Miyamoto, A., Fukunaga, T.: Effect of short-duration spaceflight on thigh and leg muscle volume. Med. Sci. Sports. Exerc. 32(10), 1743–1747 (2000)

    Article  Google Scholar 

  • Arai, M., Kurokawa, I., Arakane, H., Kitazono, T., Ishihara, T.: Regulation of Diacylglycerol Content in Olfactory Neurons Determines Forgetting or Retrieval of Olfactory Memory in Caenorhabditis elegans. J. Neurosci. 42(43), 8039–8053 (2022)

    Article  Google Scholar 

  • Banakar, P., Hada, A., Papolu, P.K., Rao, U.: Simultaneous RNAi Knockdown of Three FMRFamide-Like Peptide Genes, Mi-flp1, Mi-flp12, and Mi-flp18 Provides Resistance to Root-Knot Nematode Meloidogyne incognita. Front. Microbiol. 11,(2020)

  • Baugh, L.R., Hu, P.J.: Starvation Responses Throughout the Caenorhabditiselegans Life Cycle. Genetics 216(4), 837–878 (2020)

    Article  Google Scholar 

  • Bessou, C., Giugia, J.B., Franks, C.J., Holden-Dye, L., Ségalat, L.: Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to hyperactivity and suggest a link with cholinergic transmission. Neurogenetics 2(1), 61–72 (1998)

    Article  Google Scholar 

  • Bouredji, Z., Argaw, A., Frenette, J.: The inflammatory response, a mixed blessing for muscle homeostasis and plasticity. Front. Physiol. 13, 1032450 (2022)

    Article  Google Scholar 

  • Brenner, J.L., Kemp, B.J., Abbott, A.L.: The mir-51 family of microRNAs functions in diverse regulatory pathways in Caenorhabditis elegans. PLoS One 7(5),(2012)

  • Clark, A.M., Goldstein, L.D., Tevlin, M., Tavaré, S., Shaham, S., Miska, E.A.: The microRNA miR-124 controls gene expression in the sensory nervous system of Caenorhabditis elegans. Nucleic. Acids Res. 38(11), 3780–3793 (2010)

    Article  Google Scholar 

  • Dexheimer, P.J., Wang, J., Cochella, L.: Two MicroRNAs Are Sufficient for Embryonic Patterning in C. elegans. Curr. Biol. 30(24), 5058-5065.e5055 (2020)

  • Feng, T., Zhang, P., Sun, Y., Han, X., Tong, J., Hua, Z.: Evaluation of the Role of hsa-mir-124 in Predicting Clinical Outcome in Breast Invasive Carcinoma Based on Bioinformatics Analysis. Biomed. Res. Int. 2020, 1839205 (2020)

    Article  Google Scholar 

  • Fitts, R.H., Riley, D.R., Widrick, J.J.: Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J. Appl. Physiol. (1985) 89(2), 823-839 (2000)

  • Gieseler, K., Grisoni, K., Ségalat, L.: Genetic suppression of phenotypes arising from mutations in dystrophin-related genes in Caenorhabditis elegans. Curr. Biol. 10(18), 1092–1097 (2000)

    Article  Google Scholar 

  • Gieseler, K., Grisoni, K., Mariol, M.C., Ségalat, L.: Overexpression of dystrobrevin delays locomotion defects and muscle degeneration in a dystrophin-deficient Caenorhabditis elegans. Neuromuscul. Disord. 12(4), 371–377 (2002)

    Article  Google Scholar 

  • Higashibata, A., Szewczyk, N.J., Conley, C.A., Imamizo-Sato, M., Higashitani, A., Ishioka, N.: Decreased expression of myogenic transcription factors and myosin heavy chains in Caenorhabditis elegans muscles developed during spaceflight. J. Exp. Biol. 209(Pt 16), 3209–3218 (2006)

    Article  Google Scholar 

  • Honda, Y., Higashibata, A., Matsunaga, Y., Yonezawa, Y., Kawano, T., Higashitani, A., Kuriyama, K., Shimazu, T., Tanaka, M., Szewczyk, N.J., Ishioka, N., Honda, S.: Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans. Sci. Rep. 2, 487 (2012)

    Article  Google Scholar 

  • Huang, Y., Day, R.N., Gunst, S.J.: Vinculin phosphorylation at Tyr1065 regulates vinculin conformation and tension development in airway smooth muscle tissues. J. Biol. Chem. 289(6), 3677–3688 (2014)

    Article  Google Scholar 

  • Ikeda, H., Muratani, M., Hidema, J., Hada, M., Fujiwara, K., Souda, H., Yoshida, Y., Takahashi, A.: Expression Profile of Cell Cycle-Related Genes in Human Fibroblasts Exposed Simultaneously to Radiation and Simulated Microgravity. Int. J. Mol. Sci. 20(19) (2019)

  • Karp, X., Hammell, M., Ow, M.C., Ambros, V.: Effect of life history on microRNA expression during C. elegans development. Rna 17(4), 639-651 (2011)

  • Kawano, F.: The mechanisms underlying neuromuscular changes in microgravity environment. Biol. Sci. Space 18(3), 104–105 (2004)

    Google Scholar 

  • Kloosterman, W.P., Plasterk, R.H.: The diverse functions of microRNAs in animal development and disease. Dev. Cell. 11(4), 441–450 (2006)

    Article  Google Scholar 

  • Laranjeiro, R., Harinath, G., Pollard, A.K., Gaffney, C.J., Deane, C.S., Vanapalli, S.A., Etheridge, T., Szewczyk, N.J., Driscoll, M.: Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult Caenorhabditis elegans. iScience 24(2), 102105 (2021)

  • Lecroisey, C., Brouilly, N., Qadota, H., Mariol, M.C., Rochette, N.C., Martin, E., Benian, G.M., Ségalat, L., Mounier, N., Gieseler, K.: ZYX-1, the unique zyxin protein of Caenorhabditis elegans, is involved in dystrophin-dependent muscle degeneration. Mol. Biol. Cell. 24(8), 1232–1249 (2013)

    Article  Google Scholar 

  • Lewis, J.A., Szilagyi, M., Gehman, E., Dennis, W.E., Jackson, D.A.: Distinct patterns of gene and protein expression elicited by organophosphorus pesticides in Caenorhabditis elegans. BMC Genomics 10, 202 (2009)

    Article  Google Scholar 

  • Li, C., Kim, K. Neuropeptides. : The C. elegans Research Community, WormBook: 10-14 (2008)

  • Liu, C., Yu, J.: Approaches to microRNA identification and function research. Beijing: Chemistry Industry Press: 41-46 (2012)

  • Lynch, A.M., Zhu, Y., Lucas, B.G., Winkelman, J.D., Bai, K., Martin, S.C.T., Block, S., Slabodnick, M.M., Audhya, A., Goldstein, B., Pettitt, J., Gardel, M.L., Hardin, J.: TES-1/Tes and ZYX-1/Zyxin protect junctional actin networks under tension during epidermal morphogenesis in the C. elegans embryo. Curr. Biol. 32(23), 5189-5199.e5186 (2022)

  • McGowan, H., Mirabella, V.R., Hamod, A., Karakhanyan, A., Mlynaryk, N., Moore, J.C., Tischfield, J.A., Hart, R.P., Pang, Z.P.: hsa-let-7c miRNA Regulates Synaptic and Neuronal Function in Human Neurons. Front. Synaptic. Neurosci. 10, 19 (2018)

    Article  Google Scholar 

  • Nelson, L.S., Rosoff, M.L., Li, C.: Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans. Science 281(5383), 1686–1690 (1998)

    Article  Google Scholar 

  • Nisaa, K., Ben-Zvi, A.: HLH-1 Modulates Muscle Proteostasis During Caenorhabditis elegans Larval Development. Front. Cell. Dev. Biol. 10,(2022)

  • Ohtsuki, T., Koga, M., Ishiguro, H., Horiuchi, Y., Arai, M., Niizato, K., Itokawa, M., Inada, T., Iwata, N., Iritani, S., Ozaki, N., Kunugi, H., Ujike, H., Watanabe, Y., Someya, T., Arinami, T.: A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia. Schizophr. Res. 101(1–3), 9–16 (2008)

    Article  Google Scholar 

  • Palmer, J.C., Baig, S., Kehoe, P.G., Love, S.: Endothelin-converting enzyme-2 is increased in Alzheimer’s disease and up-regulated by Abeta. Am. J. Pathol. 175(1), 262–270 (2009)

    Article  Google Scholar 

  • Patel, R., Galagali, H., Kim, J.K., Frand, A.R.: Feedback between a retinoid-related nuclear receptor and the let-7 microRNAs controls the pace and number of molting cycles in C. elegans. Elife 11 (2022)

  • Preu, P., Braun, M.: German SIMBOX on Chinese mission Shenzhou-8: Europe’s first bilateral cooperation utilizing China’s Shenzhou programme. Acta Astronautica 94, 584–591 (2014)

    Article  Google Scholar 

  • Qiao, L., Luo, S., Liu, Y., Li, X., Wang, G., Huang, Z.: Reproductive and locomotory capacities of Caenorhabditis elegans were not affected by simulated variable gravities and spaceflight during the Shenzhou-8 mission. Astrobiology 13(7), 617–625 (2013)

    Article  Google Scholar 

  • Rao, U., Thakur, P.K., G, N.P., Banakar, P., Kumar, M.: Identification of neuropeptides, flp-1 and flp-12 targeting neuromuscular system of rice root knot nematode (RRKN) Meloidogyne graminicola. Bioinformation 9(4), 182-186 (2013)

  • Reitz, G.: Characteristic of the radiation field in low Earth orbit and in deep space. Z Med. Phys. 18(4), 233–243 (2008)

    Article  Google Scholar 

  • Simon, D.J., Madison, J.M., Conery, A.L., Thompson-Peer, K.L., Soskis, M., Ruvkun, G.B., Kaplan, J.M., Kim, J.K.: The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions. Cell 133(5), 903–915 (2008)

    Article  Google Scholar 

  • Stefani, G., Slack, F.J.: Small non-coding RNAs in animal development. Nat. Rev. Mol. Cell Biol. 9(3), 219–230 (2008)

    Article  Google Scholar 

  • Takahashi, A., Suzuki, H., Omori, K., Seki, M., Hashizume, T., Shimazu, T., Ishioka, N., Ohnishi, T.: Expression of p53-regulated proteins in human cultured lymphoblastoid TSCE5 and WTK1 cell lines during spaceflight. J. Radiat. Res. 53(2), 168–175 (2012)

    Article  Google Scholar 

  • van Loon, J.J.W.A.: Some history and use of the random positioning machine, RPM, in gravity related research. Adv. Space Res. 39(7), 1161–1165 (2007)

    Article  Google Scholar 

  • Wang, C., Sang, C., Akira, H., Noriaki, I., Rong, L., Yang, C., Sun, Y., Yi, Z.C., Zhuang, F.Y.: Changes of Muscle–related Genes and Proteins After Spaceflight in Caenorhabditis elegans. Prog. Bioch. Bioph. 35(10), 1195–1201 (2008)

    Google Scholar 

  • Wang, S., Zheng, T., Wang, Y.: Transcription activity hot spot, is it real or an artifact? BMC Proc. 1 Suppl 1, S94 (2007)

  • Xu, D., Gao, Y., Guo, L., Xing, Y.F., Sun, Y.Q.: Effect of dys-1 mutation on gene expression profile in space-flown C. elegans. Muscle Nerve 234, 396-405 (2018)

  • Xu, D., Gao, Y., Huang, L., Sun, Y.Q.: Changes in miRNA expression profile of space-flown Caenorhabditis elegans during Shenzhou-8 mission. Life Sci. Space Res. 1, 44–52 (2014)

    Article  Google Scholar 

  • Yim, P.D., Gallos, G., Xu, D., Zhang, Y., Emala, C.W.: Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle. Faseb. J. 25(5), 1706–1717 (2011)

    Article  Google Scholar 

  • Zhou, S., Chen, L.: Neural integrity is maintained by dystrophin in C. elegans. J. Cell Biol. 192(2), 349-363 (2011)

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Acknowledgements

We acknowledge support from Space Science Experiment Project in Chinese Space Station (no. SCP03-01-02), and National Natural Science Foundation of China (no. 32071244).

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Jiahong Jiang: Writing - original draft, Methodology, Investigation, Data curation, Lei Zhao, Funding acquisition, Supervision. Lin Guo: Validation, simulated microgravity experiments, prepared figures; Yanfang Xing, Validation, miRNA expression analysis, prepared tables. Yuqing Sun: Resources, Funding acquisition, Conceptualization. Dan Xu: Writing - review & editing, Project administration, Supervision. All authors reviewed the manuscript.

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Correspondence to Dan Xu.

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Jiang, J., Zhao, L., Guo, L. et al. Integrated Analysis of MRNA and MiRNA Expression Profiles in dys-1 Mutants of C. Elegans After Spaceflight and Simulated Microgravity. Microgravity Sci. Technol. 35, 31 (2023). https://doi.org/10.1007/s12217-023-10057-w

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