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

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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.