Alu RNA modulates the expression of cell cycle genes in human fibroblasts

Simona Cantarella, Davide Carnevali, Marco Morselli, Anastasia Conti, Matteo Pellegrini, Barbara Montanini, Giorgio Dieci

Research output: Contribution to journalArticle

Abstract

Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblasts and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry. Accordingly, Alu overexpression was found to promote transition from G1 to S phase, as revealed by flow cytometry. Therefore, increased Alu RNA may contribute to sustained cell proliferation, which is an important factor of cancer development and progression.

Original languageEnglish
Article number3315
JournalInternational Journal of Molecular Sciences
Volume20
Issue number13
DOIs
Publication statusPublished - Jul 1 2019

Keywords

  • Alu retrotransposons
  • Cell cycle
  • Non-coding RNA

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Cantarella, S., Carnevali, D., Morselli, M., Conti, A., Pellegrini, M., Montanini, B., & Dieci, G. (2019). Alu RNA modulates the expression of cell cycle genes in human fibroblasts. International Journal of Molecular Sciences, 20(13), [3315]. https://doi.org/10.3390/ijms20133315