title: Developmental roles of Drosophila tRNA processing endonuclease RNase ZL as revealed with a conditional rescue system.
abstract: Drosophila RNase Z(L) (dRNaseZ) belongs to a family of endoribonucleases with a major role in tRNA 3'-end processing. The biochemical function of RNase Z(L) is conserved from yeast to human. Here we present a study of its biological function during Drosophila development. In flies, dRNaseZ provides a non-redundant function, as the RNZ(ED24) knockout (KO) mutation causes early larval lethality. Mosaic and conditional rescue techniques were employed to determine dRNaseZ requirements at later stages. We found that dRNaseZ activity is essential for all phases of fly development that involve cell division, including growth of adult tissue progenitors during larval and metamorphic stages, and gametogenesis in adults. At the cellular level, two major phenotypes were identified-cell growth deficiency in endoreplicating tissues and cell cycle arrest in mitotic tissues. While cell growth and proliferation are both dependant on protein synthesis, the two phenotypes displayed reliance on different dRNaseZ functions. We found that dRNaseZ KO completely blocks tRNA maturation without diminishing the abundance of mature tRNA molecules. Our data indicate that growth arrest of endoreplicating cells is primarily attributed to the relocation of the pool of mature tRNAs into the nuclei causing a decrease in translation efficiency. Mitotically dividing cells appear to be less dependent on translation machinery as they maintain their normal size when deprived of dRNaseZ activity, but rather display a cell cycle arrest at the G2-M transition.
authors.affiliation: Department of Biology, Fordham University, Bronx, NY 10458, USA.
authors.forename: Xie
authors.initials: X
authors.lastname: Xie
authors.forename: Veronica
authors.initials: V
authors.lastname: Dubrovskaya
authors.forename: Nancy
authors.initials: N
authors.lastname: Yacoub
authors.forename: Joanna
authors.initials: J
authors.lastname: Walska
authors.forename: Tara
authors.initials: T
authors.lastname: Gleason
authors.forename: Katherine
authors.initials: K
authors.lastname: Reid
authors.forename: Edward B
authors.initials: EB
authors.lastname: Dubrovsky
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D062951:Endoreduplication; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D055786:Gene Knockout Techniques; D008297:Male; D008938:Mitosis; D014176:Protein Biosynthesis; D034443:RNA Transport; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D012343:RNA, Transfer; D004722:Endoribonucleases; C558385:RNaseZ protein, Drosophila
keywords: Cell growth; Cell proliferation; Drosophila; RNase Z; tRNA processing