MLE/DHX9 HELICASE ACTIVITY IS REQUIRED TO REGULATE THE EXPRESSION OF A NUMBER OF TISSUE-SPECIFIC GENES ON CHROMOSOME 4 IN DROSOPHILA MELANOGASTER

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

DHX9 helicase and its ortholog MLE in D. melanogaster participate in different stages of gene expression. Both helicases are important for the formation and functioning of the nervous system in humans and D. melanogaster, respectively. However, the role of helicase activity of DHX9 and MLE in the regulation of gene expression has been poorly studied, and the existing data are quite contradictory. This work is devoted to the study of the role of helicase activity of MLE in the regulation of gene expression in D. melanogaster. On chromosome 4 of D. melanogaster, in locus 102F, a site of intense MLE binding was found. It was shown that MLE is a co-activator of expression of the Dyrk3, Toy, Sox102F, Shaven and Fuss genes located in this locus. For this, the helicase activity of MLE is required. Genes whose expression depends on MLE are expressed at a high level in the nervous system of D. melanogaster and are necessary for its proper development. The obtained data contribute to the study of potentially evolutionarily conserved functions of MLE.

About the authors

I. A Zolin

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Moscow, Russian Federation

A. A Grigel

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Moscow, Russian Federation

S. G Georgieva

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Academician of the RAS Moscow, Russian Federation

A. N Krasnov

Institute of Gene Biology, Russian Academy of Sciences

Moscow, Russian Federation

J. V Nikolenko

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: julia.v.nikolenko@gmail.com
Moscow, Russian Federation

References

  1. Lee T., Pelletier J. The biology of DHX9 and its potential as a therapeutic target. Oncotarget. 2016. Vol. 7. P. 42716–42739.
  2. Reenan R.A., Hanrahan C.J., Ganetzky B. The mienapts RNA Helicase Mutation in Drosophila Results in a Splicing Catastrophe of the para Na + Channel Transcript in a Region of RNA Editing. Neuron. 2000. Vol. 25. P. 139–149.
  3. Bratt E., Öhman M. Coordination of editing and splicing of glutamate receptor pre-mRNA. RNA. 2003. Vol. 9. P. 309–318.
  4. Samata M., Akhtar A. Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs. Annu Rev Biochem. 2018. Vol. 87. P. 323–350.
  5. Николенко Ю. В., Куриакова М. М., Краснов А. Н. и др. Хеликаза MLE – новый участник регуляции транскрипции гена ftz-f1, кодирующего ядерный рецептор у высших эукариот. Докл. Акад. Наук. Науки о жизни. 2021. Т. 496. С. 48–51.
  6. Николенко Ю. В., Георгиев С. Г. Хеликаза MLE (DHX9) регулирует экспрессию конститутивной и индуцибельной изобром консервативного ядерного рецептора FTZ-F1 (NR5A3). Молекулярная биология. 2025. Т. 59. С. 266–276.
  7. Ашниев Г. А., Георгиев С. Г., Николенко Ю. В. Функции хеликазы MLE Drosophila melanogaster вне дозовой компенсации: молекулярная природа и плейотропный эффект мутации mle[9]. Генетика. 2024. Т. 60. С. 34–46.
  8. Золин И. А., Георгиев С. Г., Николенко Ю. В. Консервативная в эволюции хеликаза DHX9/MLE участвует в регуляции уровня экспрессии мPHK собственного гена у Drosophila melanogaster. Докл. Акад. Наук. Науки о жизни. 2025. Т. 520. С. 63–67.
  9. Kotlikova I. V., Demakova O. V., Semeshin V.F., et al. The Drosophila Dosage Compensation Complex Binds to Polytene Chromosomes Independently of Developmental Changes in Transcription. Genetics. 2006. Vol. 14. P. 1478–1488.
  10. Valsechi C.I.K., Basilicata M.F., Semplicio G., et al. Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells. Nat Commun. 2018. Vol. 9(1):3626.
  11. Fergestad T., Ganetzky B., Palladino M.J. Neuropathology in Drosophila membrane excitability mutants. Genetics. 2006. Vol. 172. P. 1031–1042.
  12. Charlton-Perkins M., Whitaker S.L., Fei Y., et al. Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling. Neural Dev. 2011. Vol. 6: 20.
  13. Dimitriadou A., Chatzianastasi N., Zacharaki P.I., et al. Adult Movement Defects Associated with a CORL Mutation in Drosophila Display Behavioral Plasticity. G3 GenesGenomesGenetics, 2020. Vol. 10. №. 5. P. 1697–1706.
  14. Figueiredo M.L.A., Kim M., Philip P., et al. Non-coding roX RNAs Prevent the Binding of the MSL-complex to Heterochromatic Regions. PLoS Genet. 2014. Vol. 10(12): e1004865.
  15. Marr S.K., Lis J.T., Treisman, J.E., et al. The metazo-an-specific mediator subunit 26 (Med26) is essential for viability and is found at both active genes and pericentric heterochromatin in Drosophila melanogaster. 2014. Mol. Cell. Biol. Vol. 34. P. 2710–2720.
  16. Luebbering N., Charlton-Perkins M., Kumar J.P., et al. Drosophila dyriX plays a role in the development of the visual system. PLoS ONE. 2013. Vol. 8(10): e76775.
  17. Schilling T., Ali A.H., Leonhardt A., et al. Transcriptional control of morphological properties of direction-selective T4/T5 neurons in Drosophila. Development. 2019. Vol. 146(2):dev169763.
  18. Naidu V.G., Zhang Y., Lowe S., et al. Temporal progression of Drosophila medulla neuroblasts generates the transcription factor combination to control T1 neuron morphogenesis. Dev. Biol. 2020. Vol. 464. P. 35–44.
  19. Calame D.G., Guo T., Wang C., et al. Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease. Am J Hum Genet. 2023. Vol. 110. P. 1394–1413.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russian Academy of Sciences