Cryptococcus neoformans Slu7 ensures nuclear positioning during mitotic progression through RNA splicing.

Autor: Krishnan VP; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India., Negi MS; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India., Peesapati R; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India., Vijayraghavan U; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2024 May 20; Vol. 20 (5), pp. e1011272. Date of Electronic Publication: 2024 May 20 (Print Publication: 2024).
DOI: 10.1371/journal.pgen.1011272
Abstrakt: The position of the nucleus before it divides during mitosis is variable in different budding yeasts. Studies in the pathogenic intron-rich fungus Cryptococcus neoformans reveal that the nucleus moves entirely into the daughter bud before its division. Here, we report functions of a zinc finger motif containing spliceosome protein C. neoformans Slu7 (CnSlu7) in cell cycle progression. The budding yeast and fission yeast homologs of Slu7 have predominant roles for intron 3' splice site definition during pre-mRNA splicing. Using a conditional knockdown strategy, we show CnSlu7 is an essential factor for viability and is required for efficient cell cycle progression with major role during mitosis. Aberrant nuclear migration, including improper positioning of the nucleus as well as the spindle, were frequently observed in cells depleted of CnSlu7. However, cell cycle delays observed due to Slu7 depletion did not activate the Mad2-dependent spindle assembly checkpoint (SAC). Mining of the global transcriptome changes in the Slu7 knockdown strain identified downregulation of transcripts encoding several cell cycle regulators and cytoskeletal factors for nuclear migration, and the splicing of specific introns of these genes was CnSlu7 dependent. To test the importance of splicing activity of CnSlu7 on nuclear migration, we complemented Slu7 knockdown cells with an intron less PAC1 minigene and demonstrated that the nuclear migration defects were significantly rescued. These findings show that CnSlu7 regulates the functions of diverse cell cycle regulators and cytoskeletal components, ensuring timely cell cycle transitions and nuclear division during mitosis.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Krishnan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje