Fig. 1

Ribosome profiling of Tsc2^+/− hippocampal slices reveals RNA and RPF dysregulation. a Salient features of TSC and mGluR5 signaling. mTOR indirectly receives negative and positive signals from TSC and mGluR5, respectively. mTOR promotes translation required for mGluR5-dependent long-term depression (LTD). Dashed and solid lines indicate indirect and direct effects, respectively. The purple stars indicate SFARI autism genes. b Schematic depicting the experimental design for RNA-Seq and ribosome profiling from CA1-enriched hippocampal slices of Tsc2^+/− and wild-type littermate controls. Slices were treated with DHPG (100 µM, 5 min) or artificial cerebrospinal fluid (vehicle) and then processed for RNA-Seq and ribosome profiling. Slices from six mice were pooled per genotype and condition, and three biological replicates were performed. RPF, ribosome-protected fragment. c Normalized count plots of RNA and RPF levels for Tsc2 are shown (Wald-test for genotype comparison with BH correction. RNA: log2FC − 0.52, padj < 7.4e−32; RPF log2FC − 0.70, padj < 2.4e−22) d, e Heat maps of mRNAs (d) and RPFs (e) altered in Tsc2^+/− compared to WT under basal conditions. Relative gene expression is shown, and each column represents a biological replicate (n = 3) for RNA (DE = 109, FDR < 0.1) and RPFs (DE = 99, FDR < 0.1). f GO term enrichment of upregulated RPFs in Tsc2^+/− (padj < 0.05)