The pre-mRNA retention and splicing complex controls expression of the Mediator subunit Med20

The heterotrimeric pre-mRNA retention and splicing (RES) complex, consisting of Bud13p, Snu17p and Pml1p, promotes splicing and nuclear retention of a subset of intron-containing pre-mRNAs. Yeast cells deleted for individual RES genes show growth defects that are exacerbated at elevated temperatures. Although the growth phenotypes correlate to the splicing defects in the individual mutants, the underlying mechanism is unknown. Here, we show that the temperature sensitive (Ts) growth phenotype of <i>bud13Δ</i> and <i>snu17Δ</i> cells is a consequence of inefficient splicing of <i>MED20</i> pre-mRNA, which codes for a subunit of the Mediator complex; a co-regulator of RNA polymerase II transcription. The <i>MED20</i> pre-mRNA splicing defect is less pronounced in <i>pml1Δ</i> cells, explaining why they grow better than the other two RES mutants at elevated temperatures. Inactivation of the cytoplasmic nonsense-mediated mRNA decay (NMD) pathway in the RES mutants leads to accumulation of <i>MED20</i> pre-mRNA, indicating that inefficient nuclear retention contributes to the growth defect. Further, the Ts phenotype of <i>bud13Δ</i> and <i>snu17Δ</i> cells is partially suppressed by the inactivation of NMD, showing that the growth defects are augmented by the presence of a functional NMD pathway. Collectively, our results demonstrate an important role of the RES complex in maintaining the Med20p levels.