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Fig. 9

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ZDB-IMAGE-210925-31
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Figures for Riboldi et al., 2021
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Figure Caption

Fig. 9 SIM-less SMN fails to rescue select downstream RNA processing events disrupted by SMN deficiency in SMA mice.

a RT-qPCR analysis of aberrantly spliced Stasimon (Stas) mRNA (indicated by the red lines between exon 3 and exon 5) in the spinal cord from WT mice or SMA mice injected with AAV9-GFP, AAV9-SMN-WT, or AAV9-SMN-2VA at P9. Data represent mean and SEM (WT n = 5 animals; SMA + GFP n = 5 animals; SMA + SMN-WT n = 5 animals; SMA + SMN-2VA n = 4 animals). Statistical significance was determined by one-way ANOVA with Tukey’s post hoc test (adjusted P values: WT vs. SMA + GFP p = 0.0001; WT vs. SMA + SMN-WT p = 0.9561; WT vs. SMA + SMN-2VA p = 0.0162; SMA + GFP vs. SMA + SMN-WT p = 0.0003; SMA + GFP vs. SMA + SMN-2VA p = 0.1682; SMA + SMN-WT vs. SMA + SMN-2VA p = 0.0408). b RT-qPCR analysis of total 3′ end-extended histone H1c mRNA. Data represent mean and SEM (WT n = 5 animals; SMA + GFP n = 5 animals; SMA + SMN-WT n = 5 animals; SMA + SMN-2VA n = 4 animals). Statistical significance was determined by one-way ANOVA with Tukey’s post hoc test (adjusted P values: WT vs. SMA + GFP p < 0.0001; WT vs. SMA + SMN-WT p = 0.0827; WT vs. SMA + SMN-2VA p < 0.0001; SMA + GFP vs. SMA + SMN-WT p < 0.0001; SMA + GFP vs. SMA + SMN-2VA p = 0.0725; SMA + SMN-WT vs. SMA + SMN-2VA p = 0.0036). c Cdkn1a mRNA in the spinal cord at P9 from the same treatment groups as in (a). Data represent mean and SEM (WT n = 5 animals; SMA + GFP n = 5 animals; SMA + SMN-WT n = 5 animals; SMA + SMN-2VA n = 4 animals). Statistical significance was determined by one-way ANOVA with Tukey’s post hoc test (adjusted P values: WT vs. SMA + GFP p < 0.0001; WT vs. SMA + SMN-WT p = 0.6815; WT vs. SMA + SMN-2VA p = 0.0464; SMA + GFP vs. SMA + SMN-WT p = 0.0005; SMA + GFP vs. SMA + SMN-2VA p = 0.0319; SMA + SMN-WT vs. SMA + SMN-2VA p = 0.2841). Significant differences with WT have been reported immediately atop of each bar plot, while comparisons between the other experimental conditions have been graphed with connecting lines. d Model of the consequences of loss of SMN-SUMO interactions on the assembly and function of the SMN complex.

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