Abstract
BackgroundOne key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes (mRNPs). Formation of the mRNP requires the participation of a number of conserved factors such as the THO complex. THO interacts physically and functionally with the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein linking transcription, mRNA export and genome integrity. Given the link between genome instability and cancer, we have performed a comparative analysis of the expression patterns of THOC1, a THO complex subunit, and ALY in tumor samples.MethodsThe mRNA levels were measured by quantitative real-time PCR and hybridization of a tumor tissue cDNA array; and the protein levels and distribution by immunostaining of a custom tissue array containing a set of paraffin-embedded samples of different tumor and normal tissues followed by statistical analysis.ResultsWe show that the expression of two mRNP factors, THOC1 and ALY are altered in several tumor tissues. THOC1 mRNA and protein levels are up-regulated in ovarian and lung tumors and down-regulated in those of testis and skin, whereas ALY is altered in a wide variety of tumors. In contrast to THOC1, ALY protein is highly detected in normal proliferative cells, but poorly in high-grade cancers.ConclusionsThese results suggest a differential connection between tumorogenesis and the expression levels of human THO and ALY. This study opens the possibility of defining mRNP biogenesis factors as putative players in cell proliferation that could contribute to tumor development.
Highlights
One key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes
The results showed that both the expression of THOC1 and ALY is altered in several tumor tissues, suggesting a connection of these mRNA ribonucleoparticle complexes (mRNPs) biogenesis factors with tumorogenesis
THOC1, was taken as representative of factors that act at the transcription level such as THO-UAP56, and ALY, as a related factor that serves as adaptor in mRNA export
Summary
One key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes (mRNPs). THO interacts physically and functionally with the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein linking transcription, mRNA export and genome integrity. THO interacts physically and functionally with proteins involved in mRNA export: the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein; forming a larger complex termed TREX (transcriptionexport complex) [8]. Yeast THO, sub mutant and to a lesser extent yra mutants show similar phenotypes of transcription impairment, mRNA export defects and transcription-associated hyperrecombination which indicate that these proteins could act in the same mRNP biogenesis pathway [5,9]. THO and Sub can be considered the closest related factors, given the capacity of Sub overexpression to suppress THO mutations, and the similarity in the strength of the phenotypes conferred by hpr, tho and sub mutations [10,11]
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