Effects of ERG knockdown on HeLa cells mRNA stability

Control of mRNA levels is a fundamental aspect in the regulation of gene expression and is achieved through a balance between mRNA synthesis and decay. E-twenty-six-related gene (Erg) proteins are canonical transcription factors whose described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function. ERG is recruited to mRNAs via its interaction with the RNA-binding protein RBPMS and promotes mRNA decay by binding to CNOT2, a component of the CCR4 deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, and whose decay during S-phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation. HeLa cells treated with a control (siCTL) or anti-ERG (siERG) siRNA were transcriptionally arrested with actinomycin D for 0, 0.5, 1, 2 and 4h. Total RNA was extracted at each time point (T0, T0.5, T1, T2 and T4) and were anaysed using HumanHT-12 v4 BeadChip . Analysis were performed on four biological replicates.