SRSF3 depletion in MKs results in aberrant loading of RNA into platelets. (A) Relative RNA content of control and Pf4-Srsf3^Δ/Δ MKs and platelets (n = 3-6). (B) Volcano plot depicting differential RNA repertoire between control and Pf4-Srsf3^Δ/Δ platelets. The data points marked with blue were significantly less abundant in Pf4-Srsf3^Δ/Δ platelets, and the points marked in red were more abundant when compared with control (FDR <0.05, FC >2). (C) Pearson correlation between DEGs during MK maturation (FDR <0.05, FC = 2) and platelet RNA levels. (D-E) Frequency distribution histograms of platelet/MK RNA abundance ratio (platelet CPM/MK ≥16N CPM) in control and Pf4-Srsf3^Δ/Δ. The dotted line marks 0. (F) Levels of RNAs encoding proteins central for platelet function in control and Pf4-Srsf3^Δ/Δ 8N and ≥16N MKs and platelets. (G) A schematic depicting how SRSF3 governs a MK maturation program through RNA regulatory mechanisms such as mRNA export and guides the deposition of RNA into platelets. In the schematic, the black lines represent SRSF3 target RNAs in MKs, white lines, other MK RNAs and green balls are SRSF3. The data in panels A and F is presented as mean plus or minus SEM. Two-tailed unpaired Student t test; *P ≤ .05. CPM; counts per million; PLT, platelet.