Extended Data Fig. 4: Transcripts bound by SMN-primed ribosomes display defects in positioning of active ribosomes at early stages of SMA.
From: SMN-primed ribosomes modulate the translation of transcripts related to spinal muscular atrophy
a, mTORC1 is activated only at late stages of SMA. Upper panel, total proteins from brains at early and late stages of disease (SMA) and from littermate controls (Ctrl) were probed for phosphorylation responses by immunoblotting of known mTORC1 downstream targets (4E-BP) and PERK (eIF2a). In the right panels the quantification for 4E-BP is shown as the average signal ± SEM among n=3 biologically independent samples (normalized to total protein stain, not shown). The statistical significance from one-way ANOVA with Tukey’s multiple comparisons test is reported. b, Fraction of ribosomes in polysomes obtained from polysomal profiling of control and SMA mouse brain at early stage of disease (P5). The data represent the average ± SEM (n = 3 mice). Significant decreases were tested by two-sided t-test. c, Pairwise correlations of RPKM per protein coding transcripts (n=49825 mRNAs) between the two replicas of control and SMA Active-RiboSeq and control RiboSeq (upper panels) and between the three replicas of control SMN-specific RiboSeq (lower panels). Pearson’s correlation coefficients and statistical significance from two-sided Williams’ test are shown (*** pvalue < 1e-16). d, Over-representation of tissue-specific markers among genes with significantly increased (yellow) or decreased (red) active ribosome occupancies in SMA. Tissues where SMN levels were previously measured are displayed in bold. The enrichment score was calculated with enrichR. Statistical source data and unprocessed blots are provided in Source data Extended data Fig. 4.
