Abstract
The closely regulated process of mRNA translation is crucial for precise control of protein abundance and quality. Ribosome profiling, a combination of ribosome foot-printing and RNA deep sequencing, has been used in a large variety of studies to quantify genome-wide mRNA translation. Here, we developed Xtail, an analysis pipeline tailored for ribosome profiling data that comprehensively and accurately identifies differentially translated genes in pairwise comparisons. Applied on simulated and real datasets, Xtail exhibits high sensitivity with minimal false-positive rates, outperforming existing methods in the accuracy of quantifying differential translations. With published ribosome profiling datasets, Xtail does not only reveal differentially translated genes that make biological sense, but also uncovers new events of differential translation in human cancer cells on mTOR signalling perturbation and in human primary macrophages on interferon gamma (IFN-γ) treatment. This demonstrates the value of Xtail in providing novel insights into the molecular mechanisms that involve translational dysregulations.
Highlights
The closely regulated process of messenger RNA (mRNA) translation is crucial for precise control of protein abundance and quality
In a comparison between two conditions, differential translation can be characterized by the dissimilarity between the changes in mRNA and RPF expressions across the two conditions
We examined the results of the differential translation analysis with the PC3 data, to pursue novel biological insights into the translational dysregulations involved in mammalian target of rapamycin (mTOR) inhibition by PP242 in prostate cancer cells
Summary
The closely regulated process of mRNA translation is crucial for precise control of protein abundance and quality. Ever since the emergence of ribosome profiling, this powerful technique has been widely applied to study a variety of cellular activities in various organisms and contexts, for example, the adaptation of yeast to amino acid starvation[7] and oxidative stress[9], the effects of microRNAs on translation and mRNA decay in zebrafish[4] and human cells[10], and the molecular responses of human and mouse cells to proteotoxic stress[11], heat shock[12] and perturbations of multiple signalling processes[5,13,14] To date, these studies have produced more than 100 ribosome profiling datasets, which are highly valuable resources for understanding translational regulations in a multitude of contexts. The advantage of ribosome profiling as a genome-wide assessment of gene translation has not been fully exploited to derive a comprehensive understanding of translational regulations
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