Expression of Drosophila VDRC GD RNAi lines in larval skeletal muscle often leads to abnormal proteostasis.

In Drosophila , multiple transgenic RNAi libraries have been generated to facilitate large-scale genetic screens in vivo . Although those libraries have helped generate many new discoveries, certain libraries are associated with technical drawbacks requiring caution in interpreting the results. Here, we report an unexpected effect of VDRC GD lines on proteostasis. When expressed in the larval skeletal muscle, 17 out of 20 GD lines induced protein aggregates enriched around the myonuclei while VDRC KK or TRiP counterparts had no effect. By contrast, the same GD lines failed to induce protein aggregates when expressed in the epidermal cells. Because the GD lines tested in this study target diverse classes of molecules and since the KK or TRiP counterparts exhibited no effect, we conclude that VDRC GD lines, for unknown reasons, tend to interfere with proteostasis in a tissue-specific and target-independent manner.