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

在mRNA降解期间，Dcp 2和DcpS脱帽酶从转录物中除去5' mRNA帽结构。这两种酶的底物都是加帽的RNA，然而，Dcp 2对长转录物最具活性，而DcpS仅对短转录物有活性。在这里，我们将结合联合收割机精确的mRNA去帽分析与几种生物物理方法，以解开的“分子统治者”内的Dcp 2和DcpS酶的结构基础。此外，我们将解决这些酶的底物特异性是如何通过与开盖因子的相互作用和导致细胞加工体形成的液-液相分离来调节的。我们的见解具有重要意义，因为mRNA底物的错误脱帽将导致基因表达的显著失调。

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.