Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells

Abstract

BackgroundThe classical view on eukaryotic gene expression proposes the scheme of a forward flow for which fluctuations in mRNA levels upon a stimulus contribute to determine variations in mRNA availability for translation. Here we address this issue by simultaneously profiling with microarrays the total mRNAs (the transcriptome) and the polysome-associated mRNAs (the translatome) after EGF treatment of human cells, and extending the analysis to other 19 different transcriptome/translatome comparisons in mammalian cells following different stimuli or undergoing cell programs.ResultsTriggering of the EGF pathway results in an early induction of transcriptome and translatome changes, but 90% of the significant variation is limited to the translatome and the degree of concordant changes is less than 5%. The survey of other 19 different transcriptome/translatome comparisons shows that extensive uncoupling is a general rule, in terms of both RNA movements and inferred cell activities, with a strong tendency of translation-related genes to be controlled purely at the translational level. By different statistical approaches, we finally provide evidence of the lack of dependence between changes at the transcriptome and translatome levels.ConclusionsWe propose a model of diffused independency between variation in transcript abundances and variation in their engagement on polysomes, which implies the existence of specific mechanisms to couple these two ways of regulating gene expression.

Translational Downregulation of HSP90 Expression by Iron Chelators in Neuroblastoma Cells

“…5A). Interestingly, CPX treatment resulted in marked fluctuations of the inducible HSP72 mRNA at the transcriptome level, while the changes at the level of translatome were somewhat buffered, again exemplifying the general uncoupling between transcriptome and translatome responses (Tebaldi et al, 2012). At the protein level, CPX caused a robust reduction of HSP90 expression (Fig.…”

“…To enable a comprehensive overview of the gene expression response upon CPX treatment, a genome-wide multilevel transcriptome and translatome analysis was performed (Arava et al, 2003;Tebaldi et al, 2012). The polysomal mRNA (i.e., the mRNAs engaged in translation -the translatome) and the total mRNA (the total amount of transcribed mRNAs-the transcriptome) from CHP134 control cells and cells treated with 5 mM CPX for 90 minutes were extracted and quantified with gene expression microarrays.…”

Posttranscriptional and Translational Control of Gene Regulation in CD4+ T Cell Subsets

“…Microarray technologies assessing global mRNA levels in cells are only partially valid because posttranscriptional mechanisms dramatically affect protein levels in the proteome. Recent studies showed that ∼30% of protein levels actually correspond to mRNA levels at steady-state, suggesting that mechanisms solely regulating gene transcription or mRNA stability do not necessarily affect protein levels in cells and that changes in mRNA expression profiles frequently do not correspond to those seen in the cell's proteome (5,6).…”

Anti-inflammatory effects of alpinone 3-acetate from Alpinia japonica seeds

“…Therefore, the ''translatome'' is increasingly investigated using analytical approaches that provide substantial and somewhat surprising new information [5]. The translatome represents an intermediate level in the regulation of gene expression, between the transcriptome and proteome, and reflects interactions of mRNAs with polysomes [6]. Techniques for translatome analyses include polysome [5] and ribosome profiling (ribosome protection assays) [1,7].…”