Figure 1

Wide-scale exploration of patterns of transcriptional and translational regulation in response to energy and oncogenic stresses using RNA-Seq and Ribo-Seq. (A) We profiled gene-expression levels (RNA-Seq) and rates of mRNA translation (Ribo-Seq) in human primary fibroblast BJ cells subjected to serum depletion (energy stress which results in quiescence (Q) or induction of RAS^G12V (oncogenic stress which results in senescence (S) in the presence of functional p53, and in neoplastic transformation (T) in the absence of functional p53 and p16^INK4A). We examined the effect of RAS^G12V at two time points, 5 days (pre-senescence; preS) and 14 days (senescence; S). (B-D) Transcripts that showed either differential expression or differential translation efficiency (TE) were identified in the combined RNA-Seq and Ribo-Seq dataset and subjected to cluster analysis. Major patterns of RNA induction (B), RNA repression (C) and modulation of TE (D) were detected. Each cluster is represented by the mean pattern of its assigned transcripts (error bars represent ±SD). The first five points (red) represent transcript levels and the subsequent five points (blue) represent mRNA translation levels. Prior to clustering, levels measured for each transcript were standardized to mean = 0 and SD = 1 (so transcripts that are clustered together show similar response pattern in our dataset but might differ in the magnitude of their response). Enriched functional categories (P-value calculated using hypergeometric tail) and selected genes are indicated next to the patterns. C, control.