Ribosome assembly begins with conversion of a polycistronic precursor into 18S, 5.8S, and 25S rRNAs. In the ascomycete fungus Candida albicans, rRNA transcription starts 604 nt upstream of the 18S rRNA junction (site A1). One major internal processing site in the 5'external transcribed spacer (A0) occurs 108 nt from site A1. The A0-A1 fragment persists as a stable species during log phase growth and can be used to assess proliferation rates. Separation of the small and large subunit pre-rRNAs occurs at sites A2 and A3 in internal transcribed spacer-1 Saccharomyces cerevisiae pre-rRNA. However, the 5'end of the 5.8S rRNA is represented by only a 5.8S (S) form, and a 7S rRNA precursor of the 5.8S rRNA extends into internal transcribed spacer 1 to site A2, which differs from S. cerevisiae. External transcribed spacer 1 and internal transcribed spacers 1 and 2 show remarkable structural similarity with S. cerevisiae despite low sequence identity. Maturation of C. albicans rRNA resembles other eukaryotes in that processing can occur cotranscriptionally or post-transcriptionally. During rapid proliferation, U3 snoRNA-dependent processing occurs before large and small subunit rRNA separation, consistent with cotranscriptional processing. As cells pass the diauxic transition, the 18S pre-rRNA accumulates into stationary phase as a 23S species, possessing an intact 5'external transcribed spacer extending to site A3. Nutrient addition to starved cells results in the disappearance of the 23S rRNA, indicating a potential role in normal physiology. Therefore, C. albicans reveals new mechanisms that regulate post- versus cotranscriptional rRNA processing.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIASC009173-24
Application #
8554029
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2012
Total Cost
$423,296
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Navarathna, Dhammika H M L P; Pathirana, Ruvini U; Lionakis, Michail S et al. (2016) Candida albicans ISW2 Regulates Chlamydospore Suspensor Cell Formation and Virulence In Vivo in a Mouse Model of Disseminated Candidiasis. PLoS One 11:e0164449
Navarathna, Dhammika H; Roberts, David D; Munasinghe, Jeeva et al. (2016) Imaging Candida Infections in the Host. Methods Mol Biol 1356:69-78
Navarathna, Dhammika H M L P; Stein, Erica V; Lessey-Morillon, Elizabeth C et al. (2015) CD47 Promotes Protective Innate and Adaptive Immunity in a Mouse Model of Disseminated Candidiasis. PLoS One 10:e0128220
Pendrak, Michael L; Roberts, David D (2015) Hbr1 Activates and Represses Hyphal Growth in Candida albicans and Regulates Fungal Morphogenesis under Embedded Conditions. PLoS One 10:e0126919
Navarathna, Dhammika H M L P; Munasinghe, Jeeva; Lizak, Martin J et al. (2013) MRI confirms loss of blood-brain barrier integrity in a mouse model of disseminated candidiasis. NMR Biomed 26:1125-34
Navarathna, Dhammika H M L P; Lionakis, Michail S; Lizak, Martin J et al. (2012) Urea amidolyase (DUR1,2) contributes to virulence and kidney pathogenesis of Candida albicans. PLoS One 7:e48475
Martin-Manso, Gema; Navarathna, Dhammika H M L P; Galli, Susana et al. (2012) Endogenous thrombospondin-1 regulates leukocyte recruitment and activation and accelerates death from systemic candidiasis. PLoS One 7:e48775
Peterson, Alexander W; Pendrak, Michael L; Roberts, David D (2011) ATP binding to hemoglobin response gene 1 protein is necessary for regulation of the mating type locus in Candida albicans. J Biol Chem 286:13914-24
Navarathna, Dhammika H M L P; Das, Aditi; Morschhauser, Joachim et al. (2011) Dur3 is the major urea transporter in Candida albicans and is co-regulated with the urea amidolyase Dur1,2. Microbiology 157:270-9
Pendrak, Michael L; Roberts, David D (2011) Ribosomal RNA processing in Candida albicans. RNA 17:2235-48

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