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Bioinformatic analysis of the nucleolus.

ABSTRACT: The nucleolus is a plurifunctional, nuclear organelle, which is responsible for ribosome biogenesis and many other functions in eukaryotes, including RNA processing, viral replication and tumour suppression. Our knowledge of the human nucleolar proteome has been expanded dramatically by the two recent MS studies on isolated nucleoli from HeLa cells [Andersen, Lyon, Fox, Leung, Lam, Steen, Mann and Lamond (2002) Curr. Biol. 12, 1-11; Scherl, Coute, Deon, Calle, Kindbeiter, Sanchez, Greco, Hochstrasser and Diaz (2002) Mol. Biol. Cell 13, 4100-4109]. Nearly 400 proteins were identified within the nucleolar proteome so far in humans. Approx. 12% of the identified proteins were previously shown to be nucleolar in human cells and, as expected, nearly all of the known housekeeping proteins required for ribosome biogenesis were identified in these analyses. Surprisingly, approx. 30% represented either novel or uncharacterized proteins. This review focuses on how to apply the derived knowledge of this newly recognized nucleolar proteome, such as their amino acid/peptide composition and their homologies across species, to explore the function and dynamics of the nucleolus, and suggests ways to identify, in silico, possible functions of the novel/uncharacterized proteins and potential interaction networks within the human nucleolus, or between the nucleolus and other nuclear organelles, by drawing resources from the public domain.

SUBMITTER: Leung AK

PROVIDER: S-EPMC1223824 | biostudies-literature | 2003 Dec

REPOSITORIES: biostudies-literature

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Bioinformatic analysis of the nucleolus.

Leung Anthony K L AK Andersen Jens S JS Mann Matthias M Lamond Angus I AI

The Biochemical journal 20031201 Pt 3

The nucleolus is a plurifunctional, nuclear organelle, which is responsible for ribosome biogenesis and many other functions in eukaryotes, including RNA processing, viral replication and tumour suppression. Our knowledge of the human nucleolar proteome has been expanded dramatically by the two recent MS studies on isolated nucleoli from HeLa cells [Andersen, Lyon, Fox, Leung, Lam, Steen, Mann and Lamond (2002) Curr. Biol. 12, 1-11; Scherl, Coute, Deon, Calle, Kindbeiter, Sanchez, Greco, Hochstr ...[more]

PMID: 14531731

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Project description:Breast cancer is one of the main causes of death among women. RNA binding proteins (RBPs) play a crucial role in the progression of breast cancer, with increasingly detailed understanding of RBP functional molecular mechanisms in breast cancer, the functional research of RBPs may help elucidate the potential mechanisms of tumor occurrence, development, invasion, metastasis and prognosis. DDB1- and CUL4-associated factor 13 (DCAF13) is an RBPs has been identified as a substrate receptor for the CUL4-DDB1 E3 ligase complex. Its expression is related to the prognosis of certain cancer. We tried to explore both co-expressed network and biological functions of DCAF13 in breast cancer. The Cancer Genome Atlas (TCGA) database was used to analyze the different expression of DCAF13 messenger RNA (mRNA) between normal breast tissue and breast carcinoma tissue, and the clinical data about 960 samples were downloaded from the cBio Cancer Genomics Portal (cBioPortal). The expression level of DCAF13, co-expression network, and survival were analyzed. Those with a fold change ≥1 and FDR <0.05 were considered to have statistical significance. Unsupervised clustering of differentially expressed RBPs was performed based on log2-transformed FPKM values using the "pheatmap" package in R. Genes with a Spearman score >0.55 were regarded as moderately co-expressed genes. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a co-expression network. Meanwhile, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify the biological process cluster and pathway cluster, respectively. Compared with normal breast tissue, DCAF13 mRNA expression was significantly increased in breast cancer tissue (P<0.01). The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to identify the functions of the co-expressed network. These genes were mainly enriched in mitosis, nuclear division, metabolic process, recombination, replication and repair of DNA, double-strand break repair, posttranscriptional regulation of gene expression, regulation of cell cycle, division and proliferation, regulation of protein stability and also participation in in regulation of poly(A) RNA binding, mRNA binding, tRNA binding, adenosine triphosphate (ATP) binding. KEGG pathway analysis revealed that the genes were mainly enriched in cell cycle, oocyte meiosis and oxidative phosphorylation. According to survival analysis, upregulation of DCAF13 mRNA was significant for overall survival (OS) (P=0.0163). DCAF13 is up-regulated in breast cancer, the OS of patients with DCAF13 up-regulation was obviously reduced. DCAF13 was used as a diagnostic marker and therapeutic target for breast cancer. By building a co-expression network of DCAF13 and conducting bioinformatics analysis, it is possible to find the biomarker to evaluate patient prognosis. This finding provides a new target in mechanism and cell research of breast cancer.

Dataset Information

Bioinformatic analysis of the nucleolus.

Publications

Bioinformatic analysis of the nucleolus.

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