Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/73991
Title: Discovery of a Splicing Regulator Required for Cell Cycle Progression
Authors: Suvorova, Elena S.
Croken, Matthew
Kratzer, Stella
Ting, Li-Min
Conde De Felipe, Magnolia María 
Balu, Bharath
Markillie, Meng L.
Weiss, Louis M.
Kim, Kami
White, Michael W.
UNESCO Clasification: 310907 Patología
320712 Parasitología
Keywords: Parasite Toxoplasma-Gondii
Gene-Expression
Fission Yeast
Saccharomyces-Cerevisiae
Division Cycle
Plasmodium
Protein
Identification
Spliceosome
Proteomics
Issue Date: 2013
Journal: PLoS Genetics 
Abstract: In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.
URI: http://hdl.handle.net/10553/73991
ISSN: 1553-7390
DOI: 10.1371/journal.pgen.1003305
Source: Plos Genetics [ISSN 1553-7404], v. 9 (2), e1003305, (Febrero 2013)
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