title: The human nucleolar protein FTSJ3 associates with NIP7 and functions in pre-rRNA processing.
abstract: NIP7 is one of the many trans-acting factors required for eukaryotic ribosome biogenesis, which interacts with nascent pre-ribosomal particles and dissociates as they complete maturation and are exported to the cytoplasm. By using conditional knockdown, we have shown previously that yeast Nip7p is required primarily for 60S subunit synthesis while human NIP7 is involved in the biogenesis of 40S subunit. This raised the possibility that human NIP7 interacts with a different set of proteins as compared to the yeast protein. By using the yeast two-hybrid system we identified FTSJ3, a putative ortholog of yeast Spb1p, as a human NIP7-interacting protein. A functional association between NIP7 and FTSJ3 is further supported by colocalization and coimmunoprecipitation analyses. Conditional knockdown revealed that depletion of FTSJ3 affects cell proliferation and causes pre-rRNA processing defects. The major pre-rRNA processing defect involves accumulation of the 34S pre-rRNA encompassing from site A' to site 2b. Accumulation of this pre-rRNA indicates that processing of sites A0, 1 and 2 are slower in cells depleted of FTSJ3 and implicates FTSJ3 in the pathway leading to 18S rRNA maturation as observed previously for NIP7. The results presented in this work indicate a close functional interaction between NIP7 and FTSJ3 during pre-rRNA processing and show that FTSJ3 participates in ribosome synthesis in human cells.
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Morello
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Coltri
authors.forename: Alexandre J C
authors.initials: AJ
authors.lastname: Quaresma
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Simabuco
authors.forename: Tereza C L
authors.initials: TC
authors.lastname: Silva
authors.forename: Guramrit
authors.initials: G
authors.lastname: Singh
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Nickerson
authors.forename: Carla C
authors.initials: CC
authors.lastname: Oliveira
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Nilson I T
authors.initials: NI
authors.lastname: Zanchin
mesh_terms: D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007700:Kinetics; D008780:Methyltransferases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D034622:RNA Interference / Q000187:drug effects; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: C499553:NIP7 protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D012313:RNA; C574541:FTSJ3 protein, human; D008780:Methyltransferases; D004318:Doxycycline