A comprehensive in silico expression analysis of RNA binding proteins in normal and tumor tissue; identification of potential players in tumor formation

Abstract

RNA binding proteins (RBPs) are involved in several posttranscriptional stages of gene expression and dictate the quality and quantity of the cellular proteome. When aberrantly expressed, they can lead to disease states as well as cancers. A basic requirement to understand their role in normal tissue development and cancer is the build of comprehensive gene expression maps. In this direction, we generated a list with 383 human RBPs based on the NCBI and EMSEMBL databases. SAGE and MPSS were then used to verify their levels of expression in normal tissues while SAGE and microarray datasets were used to perform comparisons between normal and tumor tissues. As main outcomes of our studies, we identified clusters of co-expressed or co-regulated genes that could act together in the development and maintenance of specific tissues; we also obtained a high confidence list of RBPs aberrantly expressed in several tumor types. This later list contains potential candidates to be explored as diagnostic and prognostic markers as well as putative targets for cancer therapy approaches.

CD22 EXON 12 deletion as a pathogenic mechanism of human B-precursor leukemia

“…RNA splicing requires a complex interplay of multiple RNA-binding proteins that are equipped with domains to bind sequence motifs on single stranded RNA to ensure accurate determination of exon recognition. In silico interrogation of the wild-type pre-mRNA segment derived from the 132-bp mutation-rich intronic sequence between exons 12 and 13 for accessible splicing factor binding sites resulted in identification of multiple potential binding sites for the RNA-binding proteins hnRNP-E2/ PCBP, hnRNP-I/PTB, and hnRNP-L, three members of the heterogenous nuclear ribonucleoprotein family of splicing factors that act as global regulators of alternative splicing and are abundantly expressed in infant leukemias (40)(41)(42)(43)(44)(45)(46)(47)(48)(49) (Fig. 2A.1).…”

Alternative splicing and breast cancer

“…New evidences indicate that the splicing machinery is altered in cancer. 18,[85][86][87][88] For example, André and collaborators have reported the overexpression of 14 genes involved in splicing by comparing a large collection of malignant and benign breast lesions. 63 Furthermore, several SR-related proteins, including SRp40, SRp55 and TRA2-b1 have been shown to be overexpressed in breast cancer.…”

The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs

“…RBPs can contribute or lead to tumor formation when aberrantly expressed as they can interfere with the expression of specific gene subsets in cell cycle control, proliferation, apoptosis and differentiation. 1,2 Musashi1 (Msi1) is an RBP that has been connected to the development of multiple tumor types. [3][4][5][6][7][8][9] Msi1 is evolutionarily conserved, being initially identified in Drosophila melanogaster where it is required for development of adult external sensory organs (sensilla) and for maintenance of germ-line stem cell identity.…”