How do the decapping enzymes DcpS and Dcp2 sense the length of the mRNA substrate? (B12)

• Subject Area: Structural Biology
• Term: from 2017 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 185476941

During mRNA degradation the Dcp2 and DcpS decapping enzymes remove the 5’ mRNA cap structure from the transcript. The substrate for both enzymes is capped RNA, however, Dcp2 is most active on long transcripts, whereas DcpS is only active on short transcripts. Here, we will combine accurate mRNA decapping assays with several biophysical methods to unravel the structural basis for the “molecular rulers” within the Dcp2 and DcpS enzymes. In addition, we will address how the substrate specificity of these enzymes is modulated by interactions with decapping factors and by liquid-liquid phase separations that result in the formation of cellular processing bodies. Our insights have important implications, as the erroneous decapping of an mRNA substrate would lead to significant deregulation of gene expression.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 960: Ribosome Formation: Principles of RNP Biogenesis and Control of their Function
• Applicant Institution: Universität Regensburg
• Project Head: Professor Dr. Remco Sprangers