Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The Role of mRNA Quality Control in the Aging of Caenorhabditis elegans

  • Hyunwoo C. Kwon (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Yunkyu Bae (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Seung-Jae V. Lee (Department of Biological Sciences, Korea Advanced Institute of Science and Technology)
  • Received : 2023.06.27
  • Accepted : 2023.09.02
  • Published : 2023.11.30
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Abstract

The proper maintenance of mRNA quality that is regulated by diverse surveillance pathways is essential for cellular homeostasis and is highly conserved among eukaryotes. Here, we review findings regarding the role of mRNA quality control in the aging and longevity of Caenorhabditis elegans, an outstanding model for aging research. We discuss the recently discovered functions of the proper regulation of nonsense-mediated mRNA decay, ribosome-associated quality control, and mRNA splicing in the aging of C. elegans. We describe how mRNA quality control contributes to longevity conferred by various regimens, including inhibition of insulin/insulin-like growth factor 1 (IGF-1) signaling, dietary restriction, and reduced mechanistic target of rapamycin signaling. This review provides valuable information regarding the relationship between the mRNA quality control and aging in C. elegans, which may lead to insights into healthy longevity in complex organisms, including humans.

Keywords

Acknowledgement

We thank all Lee laboratory members for helpful comments and discussion. This research was supported by the KAIST Key Research Institutes Project (Interdisciplinary Research Group) to S.J.V.L.

References

  1. Amrit, F.R., Steenkiste, E.M., Ratnappan, R., Chen, S.W., McClendon, T.B., Kostka, D., Yanowitz, J., Olsen, C.P., and Ghazi, A. (2016). DAF-16 and TCER1 facilitate adaptation to germline loss by restoring lipid homeostasis and repressing reproductive physiology in C. elegans. PLoS Genet. 12, e1005788.
  2. Amrit, F.R.G., Naim, N., Ratnappan, R., Loose, J., Mason, C., Steenberge, L., McClendon, B.T., Wang, G., Driscoll, M., Yanowitz, J.L., et al. (2019). The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity. Nat. Commun. 10, 3042.
  3. Angarola, B.L. and Anczukow, O. (2021). Splicing alterations in healthy aging and disease. Wiley Interdiscip. Rev. RNA 12, e1643.
  4. Barmada, S.J., Ju, S., Arjun, A., Batarse, A., Archbold, H.C., Peisach, D., Li, X., Zhang, Y., Tank, E.M., Qiu, H., et al. (2015). Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proc. Natl. Acad. Sci. U. S. A. 112, 7821-7826.
  5. Behm-Ansmant, I., Kashima, I., Rehwinkel, J., Sauliere, J., Wittkopp, N., and Izaurralde, E. (2007). mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Lett. 581, 2845-2853.
  6. Bhadra, M., Howell, P., Dutta, S., Heintz, C., and Mair, W.B. (2020). Alternative splicing in aging and longevity. Hum. Genet. 139, 357-369.
  7. Blackwell, T.K., Sewell, A.K., Wu, Z., and Han, M. (2019). TOR signaling in Caenorhabditis elegans development, metabolism, and aging. Genetics 213, 329-360.
  8. Brandman, O. and Hegde, R.S. (2016). Ribosome-associated protein quality control. Nat. Struct. Mol. Biol. 23, 7-15.
  9. Cao, L., Qi, L., Zhang, L., Song, W., Yu, Y., Xu, C., Li, L., Guo, Y., Yang, L., Liu, C., et al. (2017). Human nonsense-mediated RNA decay regulates EMT by targeting the TGF-β signaling pathway in lung adenocarcinoma. Cancer Lett. 403, 246-259.
  10. Charizanis, K., Lee, K.Y., Batra, R., Goodwin, M., Zhang, C., Yuan, Y., Shiue, L., Cline, M., Scotti, M.M., Xia, G., et al. (2012). Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy. Neuron 75, 437-450.
  11. Chu, J., Hong, N.A., Masuda, C.A., Jenkins, B.V., Nelms, K.A., Goodnow, C.C., Glynne, R.J., Wu, H., Masliah, E., Joazeiro, C.A., et al. (2009). A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration. Proc. Natl. Acad. Sci. U. S. A. 106, 2097-2103.
  12. Curran, S.P. and Ruvkun, G. (2007). Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet. 3, e56.
  13. Debes, C., Papadakis, A., Gronke, S., Karalay, O., Tain, L.S., Mizi, A., Nakamura, S., Hahn, O., Weigelt, C., Josipovic, N., et al. (2023). Ageingassociated changes in transcriptional elongation influence longevity. Nature 616, 814-821.
  14. Deschenes, M. and Chabot, B. (2017). The emerging role of alternative splicing in senescence and aging. Aging Cell 16, 918-933.
  15. Fontana, L., Partridge, L., and Longo, V.D. (2010). Extending healthy life span--from yeast to humans. Science 328, 321-326.
  16. Ghazi, A., Henis-Korenblit, S., and Kenyon, C. (2009). A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans. PLoS Genet. 5, e1000639.
  17. Giovannone, B., Tsiaras, W.G., de la Monte, S., Klysik, J., Lautier, C., Karashchuk, G., Goldwurm, S., and Smith, R.J. (2009). GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling. Hum. Mol. Genet. 18, 4629-4639.
  18. Ham, S., Kim, S.S., Park, S., Kim, E.J.E., Kwon, S., Park, H.H., Jung, Y., and Lee, S.V. (2022). Systematic transcriptome analysis associated with physiological and chronological aging in Caenorhabditis elegans. Genome Res. 32, 2003-2014.
  19. Ham, S. and Lee, S.V. (2020). Advances in transcriptome analysis of human brain aging. Exp. Mol. Med. 52, 1787-1797.
  20. Haynes, C.M. and Hekimi, S. (2022). Mitochondrial dysfunction, aging, and the mitochondrial unfolded protein response in Caenorhabditis elegans. Genetics 222, iyac160.
  21. Heintz, C., Doktor, T.K., Lanjuin, A., Escoubas, C., Zhang, Y., Weir, H.J., Dutta, S., Silva-Garcia, C.G., Bruun, G.H., Morantte, I., et al. (2017). Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans. Nature 541, 102-106.
  22. Hodgkin, J., Papp, A., Pulak, R., Ambros, V., and Anderson, P. (1989). A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics 123, 301-313.
  23. Holly, A.C., Melzer, D., Pilling, L.C., Fellows, A.C., Tanaka, T., Ferrucci, L., and Harries, L.W. (2013). Changes in splicing factor expression are associated with advancing age in man. Mech. Ageing Dev. 134, 356-366.
  24. Huang, W., Kew, C., Fernandes, S.A., Lohrke, A., Han, L., Demetriades, C., and Antebi, A. (2022). Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity. Nat. Aging 2, 796-808.
  25. Hwang, A.B., Jeong, D.E., and Lee, S.J. (2012). Mitochondria and organismal longevity. Curr. Genomics 13, 519-532.
  26. Hwang, H.J., Park, Y., and Kim, Y.K. (2021). UPF1: from mRNA surveillance to protein quality control. Biomedicines 9, 995.
  27. Ishimura, R., Nagy, G., Dotu, I., Zhou, H., Yang, X.L., Schimmel, P., Senju, S., Nishimura, Y., Chuang, J.H., and Ackerman, S.L. (2014). RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science 345, 455-459.
  28. Jackson, K.L., Dayton, R.D., Orchard, E.A., Ju, S., Ringe, D., Petsko, G.A., Maquat, L.E., and Klein, R.L. (2015). Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther. 22, 20-28.
  29. Jang, K.H., Heras, C.R., and Lee, G. (2022). m6A in the signal transduction network. Mol. Cells 45, 435-443.
  30. Joazeiro, C.A.P. (2019). Mechanisms and functions of ribosome-associated protein quality control. Nat. Rev. Mol. Cell Biol. 20, 368-383.
  31. Ju, S., Tardiff, D.F., Han, H., Divya, K., Zhong, Q., Maquat, L.E., Bosco, D.A., Hayward, L.J., Brown, R.H., Jr., Lindquist, S., et al. (2011). A yeast model of FUS/TLS-dependent cytotoxicity. PLoS Biol. 9, e1001052.
  32. Junaid, M., Lee, A., Kim, J., Park, T.J., and Lim, S.B. (2022). Transcriptional heterogeneity of cellular senescence in cancer. Mol. Cells 45, 610-619.
  33. Jung, Y., Kwon, S., Ham, S., Lee, D., Park, H.H., Yamaoka, Y., Jeong, D.E., Artan, M., Altintas, O., Park, S., et al. (2020). Caenorhabditis elegans Lipin 1 moderates the lifespan-shortening effects of dietary glucose by maintaining ω-6 polyunsaturated fatty acids. Aging Cell 19, e13150.
  34. Kanadia, R.N., Johnstone, K.A., Mankodi, A., Lungu, C., Thornton, C.A., Esson, D., Timmers, A.M., Hauswirth, W.W., and Swanson, M.S. (2003). A muscleblind knockout model for myotonic dystrophy. Science 302, 1978-1980.
  35. Kenyon, C.J. (2010). The genetics of ageing. Nature 464, 504-512.
  36. Kim, E.J.E., Son, H.G., Park, H.H., Jung, Y., Kwon, S., and Lee, S.V. (2020). Caenorhabditis elegans algn-2 is critical for longevity conferred by enhanced nonsense-mediated mRNA decay. iScience 23, 101713.
  37. Kim, S. and Kim, C. (2021). Transcriptomic analysis of cellular senescence: one step closer to senescence atlas. Mol. Cells 44, 136-145.
  38. Kim, S.S., Sohn, J., and Lee, S.V. (2022). Immunosenescence in Caenorhabditis elegans. Immun. Ageing 19, 56.
  39. Kim, Y.K. and Maquat, L.E. (2019). UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond. RNA 25, 407-422.
  40. Lee, D., An, S.W.A., Jung, Y., Yamaoka, Y., Ryu, Y., Goh, G.Y.S., Beigi, A., Yang, J.S., Jung, G.Y., Ma, D.K., et al. (2019). MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. PLoS Biol. 17, e3000415.
  41. Lee, G.Y., Sohn, J., and Lee, S.V. (2021). Combinatorial approach using Caenorhabditis elegans and mammalian systems for aging research. Mol. Cells 44, 425-432.
  42. Lee, H. and Lee, S.V. (2022). Recent progress in regulation of aging by insulin/IGF-1 signaling in Caenorhabditis elegans. Mol. Cells 45, 763-770.
  43. Lee, Y., An, S.W.A., Artan, M., Seo, M., Hwang, A.B., Jeong, D.E., Son, H.G., Hwang, W., Lee, D., Seo, K., et al. (2015). Genes and pathways that influence longevity in Caenorhabditis elegans. In Aging Mechanisms, N. Mori and I. Mook-Jung, eds. (Tokyo, Japan: Springer), pp. 123-169.
  44. Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., and Kroemer, G. (2023). Hallmarks of aging: an expanding universe. Cell 186, 243-278.
  45. Lu, R., Chen, J., Wang, F., Wang, L., Liu, J., and Lin, Y. (2022). Lysosome inhibition reduces basal and nutrient-induced fat accumulation in Caenorhabditis elegans. Mol. Cells 45, 649-659.
  46. Ma, L., Gao, X., Luo, J., Huang, L., Teng, Y., and Horvitz, H.R. (2012). The Caenorhabditis elegans gene mfap-1 encodes a nuclear protein that affects alternative splicing. PLoS Genet. 8, e1002827.
  47. Mango, S.E. (2001). Stop making nonSense: the C. elegans smg genes. Trends Genet. 17, 646-653.
  48. Martin, P.B., Kigoshi-Tansho, Y., Sher, R.B., Ravenscroft, G., Stauffer, J.E., Kumar, R., Yonashiro, R., Muller, T., Griffith, C., Allen, W., et al. (2020). NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease. Nat. Commun. 11, 4625.
  49. Matilainen, O., Ribeiro, A.R.S., Verbeeren, J., Cetinbas, M., Sood, H., Sadreyev, R.I., and Garcia, S. (2021). Loss of muscleblind splicing factor shortens Caenorhabditis elegans lifespan by reducing the activity of p38 MAPK/PMK-1 and transcription factors ATF-7 and Nrf/SKN-1. Genetics 219, iyab114.
  50. Mazin, P., Xiong, J., Liu, X., Yan, Z., Zhang, X., Li, M., He, L., Somel, M., Yuan, Y., Phoebe Chen, Y.P., et al. (2013). Widespread splicing changes in human brain development and aging. Mol. Syst. Biol. 9, 633.
  51. Oh, C., Koh, D., Jeon, H.B., and Kim, K.M. (2022). The role of extracellular vesicles in senescence. Mol. Cells 45, 603-609.
  52. Park, J., Park, J., Lee, J., and Lim, C. (2021). The trinity of ribosomeassociated quality control and stress signaling for proteostasis and neuronal physiology. BMB Rep. 54, 439-450.
  53. Park, S., Park, H.E.H., Son, H.G., and Lee, S.J.V. (2017). The role of RNA helicases in aging and lifespan regulation. Transl. Med. Aging 1, 24-31.
  54. Powers, K.T., Szeto, J.A., and Schaffitzel, C. (2020). New insights into no-go, non-stop and nonsense-mediated mRNA decay complexes. Curr. Opin. Struct. Biol. 65, 110-118.
  55. Rimal, S., Li, Y., Vartak, R., Geng, J., Tantray, I., Li, S., Huh, S., Vogel, H., Glabe, C., Grinberg, L.T., et al. (2021). Inefficient quality control of ribosome stalling during APP synthesis generates CAT-tailed species that precipitate hallmarks of Alzheimer's disease. Acta Neuropathol. Commun. 9, 169.
  56. Rogalska, M.E., Vivori, C., and Valcarcel, J. (2023). Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Nat. Rev. Genet. 24, 251-269.
  57. Roux, A.E., Yuan, H., Podshivalova, K., Hendrickson, D., Kerr, R., Kenyon, C., and Kelley, D. (2023). Individual cell types in C. elegans age differently and activate distinct cell-protective responses. Cell Rep. 42, 112902.
  58. Sanchez-Hernandez, N., Boireau, S., Schmidt, U., Munoz-Cobo, J.P., Hernandez-Munain, C., Bertrand, E., and Sune, C. (2016). The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing. RNA 22, 571-582.
  59. Schweingruber, C., Rufener, S.C., Zund, D., Yamashita, A., and Muhlemann, O. (2013). Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells. Biochim. Biophys. Acta 1829, 612-623.
  60. Seo, M., Park, S., Nam, H.G., and Lee, S.J. (2016). RNA helicase SACY1 is required for longevity caused by various genetic perturbations in Caenorhabditis elegans. Cell Cycle 15, 1821-1829.
  61. Seo, M., Seo, K., Hwang, W., Koo, H.J., Hahm, J.H., Yang, J.S., Han, S.K., Hwang, D., Kim, S., Jang, S.K., et al. (2015). RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A. 112, E4246-E4255.
  62. Son, H.G., Altintas, O., Kim, E.J.E., Kwon, S., and Lee, S.V. (2019). Agedependent changes and biomarkers of aging in Caenorhabditis elegans. Aging Cell 18, e12853.
  63. Son, H.G. and Lee, S.V. (2017). Longevity regulation by NMD-mediated mRNA quality control. BMB Rep. 50, 160-161.
  64. Son, H.G., Seo, M., Ham, S., Hwang, W., Lee, D., An, S.W., Artan, M., Seo, K., Kaletsky, R., Arey, R.N., et al. (2017). RNA surveillance via nonsensemediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans. Nat. Commun. 8, 14749.
  65. Stein, K.C., Morales-Polanco, F., van der Lienden, J., Rainbolt, T.K., and Frydman, J. (2022). Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis. Nature 601, 637-642.
  66. Tabrez, S.S., Sharma, R.D., Jain, V., Siddiqui, A.A., and Mukhopadhyay, A. (2017). Differential alternative splicing coupled to nonsense-mediated decay of mRNA ensures dietary restriction-induced longevity. Nat. Commun. 8, 306.
  67. Tollervey, J.R., Wang, Z., Hortobagyi, T., Witten, J.T., Zarnack, K., Kayikci, M., Clark, T.A., Schweitzer, A.C., Rot, G., Curk, T., et al. (2011). Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Res. 21, 1572-1582.
  68. Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A.L., Orosz, L., and Muller, F. (2003). Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426, 620.
  69. Wang, D., Zavadil, J., Martin, L., Parisi, F., Friedman, E., Levy, D., Harding, H., Ron, D., and Gardner, L.B. (2011). Inhibition of nonsense-mediated RNA decay by the tumor microenvironment promotes tumorigenesis. Mol. Cell. Biol. 31, 3670-3680.
  70. Wang, K., Wu, D., Zhang, H., Das, A., Basu, M., Malin, J., Cao, K., and Hannenhalli, S. (2018). Comprehensive map of age-associated splicing changes across human tissues and their contributions to age-associated diseases. Sci. Rep. 8, 10929.
  71. Wu, Z., Tantray, I., Lim, J., Chen, S., Li, Y., Davis, Z., Sitron, C., Dong, J., Gispert, S., Auburger, G., et al. (2019). MISTERMINATE mechanistically links mitochondrial dysfunction with proteostasis failure. Mol. Cell 75, 835-848.e8.
  72. Yan, L.L. and Zaher, H.S. (2019). How do cells cope with RNA damage and its consequences? J. Biol. Chem. 294, 15158-15171.