title: Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition.
abstract: BACKGROUND
  Brain tumor (BRAT) is a Drosophila member of the TRIM-NHL protein family. This family is conserved among metazoans and its members function as post-transcriptional regulators. BRAT was thought to be recruited to mRNAs indirectly through interaction with the RNA-binding protein Pumilio (PUM). However, it has recently been demonstrated that BRAT directly binds to RNA. The precise sequence recognized by BRAT, the extent of BRAT-mediated regulation, and the exact roles of PUM and BRAT in post-transcriptional regulation are unknown.
  
  
  RESULTS
  Genome-wide identification of transcripts associated with BRAT or with PUM in Drosophila embryos shows that they bind largely non-overlapping sets of mRNAs. BRAT binds mRNAs that encode proteins associated with a variety of functions, many of which are distinct from those implemented by PUM-associated transcripts. Computational analysis of in vitro and in vivo data identified a novel RNA motif recognized by BRAT that confers BRAT-mediated regulation in tissue culture cells. The regulatory status of BRAT-associated mRNAs suggests a prominent role for BRAT in post-transcriptional regulation, including a previously unidentified role in transcript degradation. Transcriptomic analysis of embryos lacking functional BRAT reveals an important role in mediating the decay of hundreds of maternal mRNAs during the maternal-to-zygotic transition.
  
  
  CONCLUSIONS
  Our results represent the first genome-wide analysis of the mRNAs associated with a TRIM-NHL protein and the first identification of an RNA motif bound by this protein family. BRAT is a prominent post-transcriptional regulator in the early embryo through mechanisms that are largely independent of PUM.
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. john.laver@utoronto.ca.
authors.forename: John D
authors.initials: JD
authors.lastname: Laver
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. alicexiao.li@utoronto.ca.|Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. alicexiao.li@utoronto.ca.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. d.ray@utoronto.ca.
authors.forename: Debashish
authors.initials: D
authors.lastname: Ray
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. kathleen.cook@utoronto.ca.|Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. kathleen.cook@utoronto.ca.
authors.forename: Kate B
authors.initials: KB
authors.lastname: Cook
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. noah.hahn@mail.utoronto.ca.
authors.forename: Noah A
authors.initials: NA
authors.lastname: Hahn
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. nabeel.haidershah@mail.utoronto.ca.
authors.forename: Syed
authors.initials: S
authors.lastname: Nabeel-Shah
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. mariana.kekis@mail.utoronto.ca.|Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. mariana.kekis@mail.utoronto.ca.
authors.forename: Mariana
authors.initials: M
authors.lastname: Kekis
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. hua.luo@utoronto.ca.
authors.forename: Hua
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. alex.marsolais@mail.utoronto.ca.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Marsolais
authors.affiliation: Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. k.fung@mail.utoronto.ca.
authors.forename: Karen Yy
authors.initials: KY
authors.lastname: Fung
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. t.hughes@utoronto.ca.|Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. t.hughes@utoronto.ca.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
authors.affiliation: Department of Biology, University of Toronto, Mississauga, 3359 Mississauga Road, Mississauga, Ontario, L5L 1C6, Canada. t.westwood@utoronto.ca.
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Westwood
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. sachdev.sidhu@utoronto.ca.|Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. sachdev.sidhu@utoronto.ca.
authors.forename: Sachdev S
authors.initials: SS
authors.lastname: Sidhu
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. quaid.morris@utoronto.ca.|Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada. quaid.morris@utoronto.ca.|Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, Ontario, M5S 3G4, Canada. quaid.morris@utoronto.ca.|Department of Computer Science, University of Toronto, 40 St. George Street, Toronto, Ontario, M5S 2E4, Canada. quaid.morris@utoronto.ca.
authors.forename: Quaid
authors.initials: Q
authors.lastname: Morris
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. howard.lipshitz@utoronto.ca.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Lipshitz
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. c.smibert@utoronto.ca.|Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. c.smibert@utoronto.ca.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Smibert
mesh_terms: D000818:Animals; D001665:Binding Sites; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D063185:Epigenetic Repression; D005260:Female; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D009154:Mutation; D009687:Nuclear Proteins; D023121:RNA, Messenger, Stored / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D023121:RNA, Messenger, Stored; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C412783:brat protein, Drosophila; C074333:pum protein, Drosophila; C512295:zld protein, Drosophila