Krishnan, VP and Negi, MS and Peesapati, R and Vijayraghavan, U (2024) Cryptococcus neoformans Slu7 ensures nuclear positioning during mitotic progression through RNA splicing. In: PLoS Genetics, 20 (5 May).
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Abstract
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. © 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.
| Item Type: | Journal Article |
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| Publication: | PLoS Genetics |
| Publisher: | Public Library of Science |
| Additional Information: | The copyright for this article belongs to Authors. |
| Keywords: | BUD4 protein; CDC12 protein; CHS2 protein; DFB1 protein; dual specificity phosphatase 2; fungal protein; hydroxyurea; messenger RNA; MOB2 protein; unclassified drug, 3' untranslated region; 5' untranslated region; Article; Candida albicans; cell cycle checkpoint; cell cycle progression; cell migration; cellular, subcellular and molecular biological phenomena and functions; confocal laser scanning microscopy; confocal microscopy; Cryptococcus neoformans; Cryptococcus neoformans Slu7; down regulation; flow cytometry; gene amplification; gene expression; gene expression level; gene knockdown; live cell imaging; mitosis; nonhuman; nuclear positioning; phenotype; phylogenetic tree; polymerase chain reaction; reverse transcription polymerase chain reaction; RNA sequence; RNA splicing; Saccharomyces cerevisiae; sequence alignment; upregulation; Western blotting |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 29 Jul 2024 05:07 |
| Last Modified: | 29 Jul 2024 05:07 |
| URI: | http://eprints.iisc.ac.in/id/eprint/85182 |
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