Global mRNA polarization regulates translation efficiency in the intestinal epithelium

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Abstract

Asymmetric mRNA localization facilitates efficient translation in cells such as neurons and fibroblasts. However, the extent and significance of mRNA polarization in epithelial tissues are unclear. Here, we used single molecule transcript imaging and subcellular transcriptomics to uncover global apical-basal intracellular polarization of mRNA in the mouse intestinal epithelium. The localization of mRNAs did not generally overlap protein localization. Instead, ribosomes were more abundant on the apical sides, and apical transcripts were consequently more efficiently translated. Refeeding of fasted mice elicited a basal to apical shift in polarization of mRNAs encoding ribosomal proteins, which was associated with a specific boost in their translation. This led to increased protein production, required for efficient nutrient absorption. These findings reveal a post-transcriptional regulatory mechanism involving dynamic polarization of mRNA and polarized translation.

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Rank–rank hypergeometric overlap: identification of statistically significant overlap between gene-expression signatures

Seema B. Plaisier, Richard Taschereau, Justin A. Wong … (2010)

Comparing independent high-throughput gene-expression experiments can generate hypotheses about which gene-expression programs are shared between particular biological processes. Current techniques to compare expression profiles typically involve choosing a fixed differential expression threshold to summarize results, potentially reducing sensitivity to small but concordant changes. We present a threshold-free algorithm called Rank–rank Hypergeometric Overlap (RRHO). This algorithm steps through two gene lists ranked by the degree of differential expression observed in two profiling experiments, successively measuring the statistical significance of the number of overlapping genes. The output is a graphical map that shows the strength, pattern and bounds of correlation between two expression profiles. To demonstrate RRHO sensitivity and dynamic range, we identified shared expression networks in cancer microarray profiles driving tumor progression, stem cell properties and response to targeted kinase inhibition. We demonstrate how RRHO can be used to determine which model system or drug treatment best reflects a particular biological or disease response. The threshold-free and graphical aspects of RRHO complement other rank-based approaches such as Gene Set Enrichment Analysis (GSEA), for which RRHO is a 2D analog. Rank–rank overlap analysis is a sensitive, robust and web-accessible method for detecting and visualizing overlap trends between two complete, continuous gene-expression profiles. A web-based implementation of RRHO can be accessed at http://systems.crump.ucla.edu/rankrank/ .

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Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases.

C. Mayer, I Grummt (2006)

The target of rapamycin (TOR) signal-transduction pathway is an important mechanism by which eucaryotic cells adjust their protein biosynthetic capacity to nutrient availability. Both in yeast and in mammals, the TOR pathway regulates the synthesis of ribosomal components, including transcription and processing of pre-rRNA, expression of ribosomal proteins and the synthesis of 5S rRNA. Expression of the genes encoding the numerous constituents of ribosomes requires transcription by all three classes of nuclear RNA polymerases. In this review, we summarize recent advances in understanding the interplay among nutrient availability, transcriptional control and ribosome biogenesis. We focus on transcription in response to nutrients, detailing the relevant downstream targets of TOR in yeast and mammals. The critical role of TOR in linking environmental queues to ribosome biogenesis provides an efficient means by which cells alter their overall protein biosynthetic capacity.

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Subcellular mRNA localization in animal cells and why it matters.

E. Holt, Simon L. Bullock, Christine Elizabeth Holt (2009)

Subcellular localization of messenger RNAs (mRNAs) can give precise control over where protein products are synthesized and operate. However, just 10 years ago many in the broader cell biology community would have considered this a specialized mechanism restricted to a very small fraction of transcripts. Since then, it has become clear that subcellular targeting of mRNAs is prevalent, and there is mounting evidence for central roles for this process in many cellular events. Here, we review current knowledge of the mechanisms and functions of mRNA localization in animal cells.