title: Genome-wide screen uncovers novel pathways for tRNA processing and nuclear-cytoplasmic dynamics.
abstract: Transfer ribonucleic acids (tRNAs) are essential for protein synthesis. However, key gene products involved in tRNA biogenesis and subcellular movement remain to be discovered. We conducted the first comprehensive unbiased analysis of the role of nearly an entire proteome in tRNA biology and describe 162 novel and 12 previously known Saccharomyces cerevisiae gene products that function in tRNA processing, turnover, and subcellular movement. tRNA nuclear export is of particular interest because it is essential, but the known tRNA exporters (Los1 [exportin-t] and Msn5 [exportin-5]) are unessential. We report that mutations of CRM1 (Exportin-1), MEX67/MTR2 (TAP/p15), and five nucleoporins cause accumulation of unspliced tRNA, a hallmark of defective tRNA nuclear export. CRM1 mutation genetically interacts with los1Δ and causes altered tRNA nuclear-cytoplasmic distribution. The data implicate roles for the protein and mRNA nuclear export machineries in tRNA nuclear export. Mutations of genes encoding actin cytoskeleton components and mitochondrial outer membrane proteins also cause accumulation of unspliced tRNA, likely due to defective splicing on mitochondria. Additional gene products, such as chromatin modification enzymes, have unanticipated effects on pre-tRNA end processing. Thus, this genome-wide screen uncovered putative novel pathways for tRNA nuclear export and extensive links between tRNA biology and other aspects of cell physiology.
authors.affiliation: Department of Molecular Genetics, Center for RNA biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Molecular Genetics.
authors.forename: Alicia
authors.initials: A
authors.lastname: Bao
authors.affiliation: Department of Molecular Genetics, Center for RNA biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Kunal
authors.initials: K
authors.lastname: Chatterjee
authors.affiliation: Department of Molecular Genetics, Center for RNA biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Molecular Genetics, Center for RNA biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Anita K
authors.initials: AK
authors.lastname: Hopper
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D016681:Genome, Fungal / Q000235:genetics; D009154:Mutation; D034443:RNA Transport / Q000235:genetics; D012343:RNA, Transfer / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer
keywords: Crm1; genome-wide screen; tRNA processing; tRNA trafficking