Discovery of a splicing regulator required for cell cycle progression

dc.contributor.authorSuvorova, Elena S.
dc.contributor.authorCroken, Matthew
dc.contributor.authorKratzer, Stella
dc.contributor.authorTing, Li-Min
dc.contributor.authorConde de Felipe, Magnolia
dc.contributor.authorBalu, Bharath
dc.contributor.authorMarkillie, Meng L.
dc.contributor.authorWeiss, Louis M.
dc.contributor.authorKim, Kami
dc.contributor.authorWhite, Michael W.
dc.date.accessioned2019-04-22T19:34:27Z
dc.date.available2019-04-22T19:34:27Z
dc.date.issued2013-02
dc.description.abstractIn 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.en_US
dc.description.sponsorshipNational Institutes of Health grants R01-AI077662, R01-AI089885, RC4 AI092801, R01AI095094, T32 GM007491, Einstein-Montefiore Center for AIDS Research grant P30AI051519, Albert Einstein proteomic core facility grants 1S10RR019352, 1S10RR021056; NIH AI93220en_US
dc.identifier.citationSuvorova, Elena S., Matthew Croken, Stella Kratzer, Li-Min Ting, Magnolia Conde de Felipe, Bharath Balu, Meng L. Markillie, Louis M. Weiss, Kami Kim, and Michael W. White. “Discovery of a Splicing Regulator Required for Cell Cycle Progression.” PLoS Genetics 9, no. 2 (February 21, 2013): e1003305. doi:10.1371/journal.pgen.1003305.en_US
dc.identifier.issn1553-7404
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/15457
dc.language.isoenen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleDiscovery of a splicing regulator required for cell cycle progressionen_US
dc.typeArticleen_US
mus.citation.issue2en_US
mus.citation.journaltitlePLoS Geneticsen_US
mus.citation.volume9en_US
mus.data.thumbpage12en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1371/journal.pgen.1003305en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.relation.universityMontana State University - Bozemanen_US

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