The NIP7 protein is required for accurate pre-rRNA processing in human cells

Autor(es)

Morello, Luis G. ^[1] ; Hesling, Cedric ^{[1, 2]} ; Coltri, Patricia P. ^{[3, 1]} ; Castilho, Beatriz A. ^[3] ; Rimokh, Ruth ^[2] ; Zanchin, Nilson I. T. ^[1]

Afiliação do(s) autor(es)

^[1] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, BR-13083970 Campinas, SP - Brazil

^[2] Univ Lyon, INSERM, U590, Ctr Leon Berard, F-69373 Lyon 08 - France

^[3] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Nucleic Acids Research; v. 39, n. 2, p. 648-665, JAN 2011.
• Citações Web of Science: 13

Resumo

Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman-Bodian-Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S-80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells. (AU)

• Processo FAPESP: 06/02083-7 - Caracterização funcional de proteínas envolvidas no controle da expressão gênica
• Beneficiário: Nilson Ivo Tonin Zanchin
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/58371-3 - Determinação do papel das proteínas Ftsj3 e CXorf34 na síntese de ribossomos em células humanas
• Beneficiário: Luis Gustavo Morello
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 98/14138-2 - Center for Structural Molecular Biotechnology
• Beneficiário: Glaucius Oliva
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 06/57653-2 - Caracterização da função da proteína sbds relacionada com a síndrome de shwachman-bodian-diamond
• Beneficiário: Cédric Nicolas Patrick Hesling
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 03/06299-6 - Estudos da relação estrutura e função da proteína Nip7p e análise do seu papel no metabolismo de RNA em Saccharomyces cerevisiae e Homo sapiens
• Beneficiário: Patricia Pereira Coltri
• Linha de fomento: Bolsas no Brasil - Doutorado