Skip to main content
SpringerLink
Log in

Influence of Inactivation of Tandemly Repeated Pericentromeric DNA Transcription on the Formation of Membraneless Structures at the End of Oocyte Maturation

  • MOLECULAR BIOLOGY OF DEVELOPMENT
  • Published:
Russian Journal of Developmental Biology Aims and scope Submit manuscript

Abstract

Tandemly repeated pericentromeric noncoding DNA (TR DNA) makes up approximately 10% of the human genome. Pericentromeric TR DNA includes classical human satellites 1, 2, 3 (HS1, HS2, HS3), which are transcribed in somatic cells. We have previously shown the presence of HS2/HS3 transcripts in late human oogenesis and sequenced them. It has been suggested that the RNPs found may be the site of spatial sequestration of RNA and proteins at the end of human oocytes maturation. The aim of this work was to develop a method for inactivating HS2/HS3 transcripts using antisense oligonucleotides to assess its effect on the size and quantity of DDX4-containing RNPs in late human oogenesis. Inactivation of HS2/HS3 transcription at the end of human oocytes maturation by the microinjection method resulted in a significant decrease of the total HS2/HS3 RNA signal, detected by the method of fluorescence in situ hybridization (FISH). At the same time, an increase in the number of inclusions positive to antibodies to RNA helicase DDX4 was observed. Supposedly, upon inactivation of HS2/HS3 transcription, dissociation of DDX4-containing RNP particles occurred. Such changes of the RNP particles can play a critical role in the development of oocytes and be a cause of the arrest of maturation or the occurrence of pathological syndromes, including those associated with problems of fertilization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Banerjee, P.R., Milin, A.N., Moosa, M.M., Onuchic, P.L., and Deniz, A.A., Reentrant phase transition drives dynamic substructure formation in ribonucleoprotein droplets, Angew. Chem., Int. Ed., 2017, vol. 56, no. 38, pp. 11354–11359. https://doi.org/10.1002/anie.201703191

    Article  CAS  Google Scholar 

  2. Blanca, M.J., Alarcón, R., Arnau, J., Bono, R., and Bendayan, R., Non-normal data: is ANOVA still a valid option?, Psicothema, 2017, vol. 29, no. 4, pp. 552–557. https://doi.org/10.7334/PSICOTHEMA2016.383

    Article  PubMed  Google Scholar 

  3. Ding, Y., Chi, Y.C., and Lawrence, C.E., RNA secondary structure prediction by centroids in a Boltzmann weighted ensemble, RNA, 2005, vol. 11, no. 8, pp. 1157–1166. https://doi.org/10.1261/RNA.2500605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dobrynin, M.A. and Enukashvily, N.I., Germinal granules in animal oogenesis, Tsitologiya, 2020, vol. 62, no. 12, pp. 851–866.

    Article  Google Scholar 

  5. Dobrynin, M.A., Korchagina, N.M., Prjibelski, A.D., Shafranskaya, D., Ostromyshenskii, D.I., Shunkina, K., Stepanova, I., Kotova, A.V., Podgornaya, O.I., and Enukashvily, N.I., Human pericentromeric tandemly repeated DNA is transcribed at the end of oocyte maturation and is associated with membraneless mitochondria-associated structures, Sci. Rep., 2020, vol. 10, no. 1, pp. 1–15. https://doi.org/10.1038/s41598-020-76628-8

    Article  CAS  Google Scholar 

  6. Enukashvily, N.I. and Ponomartsev, N.V., Mammalian satellite DNA: a speaking dumb, Adv. Protein Chem. Struct. Biol., 2013, vol. 90, pp. 31–65.https://doi.org/10.1016/B978-0-12-410523-2.00002-X

    Article  CAS  PubMed  Google Scholar 

  7. Enukashvily, N.I., Dobrynin, M.A., and Chubar, A.V., Rna-seeded membraneless bodies: role of tandemly repeated RNA, Adv. Protein Chem. Struct. Biol., Academic, 2021, vol. 126, pp. 151–193. ISSN 1876-1623. https://doi.org/10.1016/bs.apcsb.2020.12.007

  8. Hubstenberger, A., Noble, S.L., Cameron, C., and Evans, T.C., Translation repressors, an RNA helicase, and developmental cues control RNP phase transitions during early development, Dev. Cell, 2013, vol. 27, no. 2, pp. 161–173. https://doi.org/10.1016/j.devcel.2013.09.024

    Article  CAS  PubMed  Google Scholar 

  9. Jain, A. and Vale, R.D., RNA phase transitions in repeat expansion disorders, Nature, 2017, vol. 546, no. 7657, pp. 243–247. https://doi.org/10.1038/nature22386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lennox, K.A. and Behlke, M.A., Chemical modification and design of anti-miRNA oligonucleotides, Gene Ther., 2011, vol. 18, no. 12, pp. 1111–1120. https://doi.org/10.1038/GT.2011.100

    Article  CAS  PubMed  Google Scholar 

  11. Maharana, S., Wang, J., Papadopoulos, D.K., Richter, D., Pozniakovsky, A., Poser, I., Bickle, M., Rizk, S., Guillen-Boixet, J., Franzmann, T.M., Jahnel, M., Marrone, L., Chang, Y.T., Sterneckert, J., Tomancak, P., Hyman, A.A., and Alberti, S., RNA buffers the phase separation behavior of prion-like RNA binding proteins, Science, 2018, vol. 360, no. 6391, pp. 918–921. https://doi.org/10.1126/SCIENCE.AAR7366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Namkoong, S., Ho, A., Woo, Y.M., Kwak, H., and Lee, J.H., Systematic characterization of stress-induced RNA granulation, Mol. Cell, 2018, vol. 70, no. 1, pp. 175–187. e8. https://doi.org/10.1016/J.MOLCEL.2018.02.025

  13. Rangan, P., DeGennaro, M., Jaime-Bustamante, K., Coux, R.-X., Martinho, R., and Lehmann, R., Temporal and spatial control of germ-plasm RNAs, Curr. Biol., 2009, vol. 19, no. 1, pp. 72–77. https://doi.org/10.1016/J.CUB.2008.11.066

    Article  CAS  PubMed  Google Scholar 

  14. Reunov, A.A. and Reunova, Y.A., In mouse oocytes the mitochondrion-originated germinal body-like structures accumulate mouse Vasa homologue (MVH) protein, Zygote, 2015, vol. 23, no. 4. https://doi.org/10.1017/S0967199414000124

  15. Rhine, K., Vidaurre, V., and Myong, S., RNA droplets, Annu. Rev. Biophys., 2020, vol. 49, p. 247. https://doi.org/10.1146/ANNUREV-BIOPHYS-052118-115508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Richard, G.-F., Kerrest, A., and Dujon, B., Comparative genomics and molecular dynamics of DNA repeats in eukaryotes, Microbiol., Mol. Biol. Rev., 2008, vol. 72, no. 4, pp. 686–727. https://doi.org/10.1128/MMBR.00011-08

    Article  CAS  Google Scholar 

  17. De Smedt, V., Szöllösi, D., and Kloc, M., The Balbiani body: asymmetry in the mammalian oocyte, Genesis, 2000, vol. 26, no. 3, p. 208. https://doi.org/10.1002/(sici)1526-968x(200003)26:3<208::aid-gene6>3.3.co;2-e

    Article  CAS  PubMed  Google Scholar 

  18. Trofimova, I.L., Enukashvily, N.I., Kuznetsova, T.V., and Baranov, V.S., Transcription of satellite DNA in human embryogenesis: literature review and own data, Med. Genet., 2018, vol. 17, no. 3, pp. 3–7.

    Google Scholar 

  19. Valgardsdottir, R., Chiodi, I., Giordano, M., Cobianchi, F., Riva, S., and Biamonti, G., Structural and functional characterization of noncoding repetitive RNAs transcribed in stressed human cells, Mol. Biol. Cell, 2005, vol. 16, no. 6, pp. 2597–2604. https://doi.org/10.1091/MBC.E04-12-1078/ASSET/IMAGES/LARGE/ZMK0060571650005.JPEG

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yandlm, C. and Karakülah, G., Expression dynamics of repetitive DNA in early human embryonic development, BMC Genomics, 2019, vol. 20. https://doi.org/10.1186/S12864-019-5803-1

Download references

Funding

The study was carried out with the financial support of a grant from the Ministry of Science and Higher Education of the Russian Federation, no. 075-15-2021-1075 dated September 28, 2021 and grant of the Russian Science Foundation, no. 19-74-20102 (collection of oocytes, design of antisense primers).

Author information

Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    M. A. Dobrynin, N. V. Ponomartsev, O. I. Podgornaya & N. I. Enukashvily

  2. Faculty of Biology, St. Petersburg State University, 199034, St. Petersburg, Russia

    N. M. Korchagina

  3. Scientific and Research Institute of Experimental Medicine, 197376, St. Petersburg, Russia

    N. M. Korchagina

Authors
  1. M. A. Dobrynin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. M. Korchagina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. V. Ponomartsev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. I. Podgornaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. I. Enukashvily
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Development of the research concept, planning of experiments: N.I. Enukashvily, N.M. Korchagina, M.A. Dobrynin; conducting experiments: M.A. Dobrynin, N.V. Korchagina; methodology: N.M. Korchagina, N.V. Ponomartsev, N.I. Enukashvily; visualization: M.A. Dobrynin; financial support: O.I. Podgornaya, N.I. Enukashvily; manuscript preparation: M.A. Dobrynin, N.I. Enukashvily.

Corresponding authors

Correspondence to M. A. Dobrynin or N. I. Enukashvily.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interests.

All oocytes were received from donors according to the order no. 803n the Ministry of Health of the Russian Federation on July 31, 2021, and in line with the Word Medical Association (WMA) Helsinki Declaration (Declaration of Helsinki: Ethical Principles for Medical Research Involving People, including the amendments to the 64th meeting of the SCA in Fortaleza, Brazil, October 2013). The study was approved by the local Ethics Committee of the Ava-Peter-Scandinavia clinics (no. 11/22-12-2016). Written informed consent was obtained from each donor included in the study.

Additional information

The data were presented at the conference of young scientists “Actual Problems of Developmental Biology” on October 12–14, 2021, Moscow, Koltzov Institute of Developmental Biology, Russian Academy of Sciences

Translated by E.N. Tolkunova

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dobrynin, M.A., Korchagina, N.M., Ponomartsev, N.V. et al. Influence of Inactivation of Tandemly Repeated Pericentromeric DNA Transcription on the Formation of Membraneless Structures at the End of Oocyte Maturation. Russ J Dev Biol 53, 128–133 (2022). https://doi.org/10.1134/S1062360422020059

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062360422020059

Keywords:

Search

Navigation