Candida albicans Dicer (CaDcr1) is required for efficient ribosomal and spliceosomal RNA maturation

被引:42
作者
Bernstein, Douglas A. [1 ]
Vyas, Valmik K. [1 ]
Weinberg, David E. [1 ,2 ,3 ]
Drinnenberg, Ines A. [1 ,3 ]
Bartel, David P. [1 ,2 ,3 ]
Fink, Gerald R. [1 ,2 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
Argonaute; CDL1; bifunctional dicer; GENE ORDER BROWSER; S-POMBE; YEAST; HOMOLOGY; CELLS; CEREVISIAE; MECHANISMS; EVOLUTION; PROTEINS; GENOME;
D O I
10.1073/pnas.1118859109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The generation of mature functional RNAs from nascent transcripts requires the precise and coordinated action of numerous RNAs and proteins. One such protein family, the ribonuclease III (RNase III) endonucleases, includes Rnt1, which functions in fungal ribosome and spliceosome biogenesis, and Dicer, which generates the siRNAs of the RNAi pathway. The recent discovery of small RNAs in Candida albicans led us to investigate the function of C. albicans Dicer (CaDcr1). CaDcr1 is capable of generating siRNAs in vitro and is required for siRNA generation in vivo. In addition, CaDCR1 complements a Dicer knockout in Saccharomyces castellii, restoring RNAi-mediated gene repression. Unexpectedly, deletion of the C. albicans CaDCR1 results in a severe slow-growth phenotype, whereas deletion of another core component of the RNAi pathway (CaAGO1) has little effect on growth, suggesting that CaDCR1 may have an essential function in addition to producing siRNAs. Indeed CaDcr1, the sole functional RNase III enzyme in C. albicans, has additional functions: it is required for cleavage of the 3' external transcribed spacer from unprocessed pre-rRNA and for processing the 3' tail of snRNA U4. Our results suggest two models whereby the RNase III enzymes of a fungal ancestor, containing both a canonical Dicer and Rnt1, evolved through a series of gene-duplication and gene-loss events to generate the variety of RNase III enzymes found in modern-day budding yeasts.
引用
收藏
页码:523 / 528
页数:6
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