Figure 1.

Structural basis of X inactivation: XIST structure and interactions. (a) Summary of mature XIST RNA structures using the human XIST as an example. XIST exons are shown as alternating black and grey rectangles (exons 2–5 are much smaller than 1 and 6). Repeat regions shown in thick blocks were annotated based on Elisaphenko et al. [9]. Each arc represents the base pairing interaction between the two arms of a duplex. Pink rectangles mark the structure domains defined by PARIS. (b) Summary of protein complexes that interact with XIST and their functions. Some of the best-studied examples of XIST interactions are shown. Short vertical arrows indicate known interactions. Question marks indicate that the mechanisms of interactions or functions remain unknown. The WTAP–RBM15–RBM15B complex primarily binds the A-repeat, but also to other regions to a minor extent. (c) The A-repeat forms stochastic inter-repeat duplexes that bind the adapter protein SPEN. (d) Consensus inter-repeat duplex model. The highlighted sequences are the two repeats. The duplex contains eight GC base pairs at the two sides and four forced base pairs in the middle, based on SHAPE reactivity. Domain model of the XIST RNP. (e) Structure model for the interaction between A-repeat and SPEN. (f) Structure model of the XIST RNP. Question marks represent interactions that are unclear or controversial. The size of each domain is not exactly scaled to the real size. The protein complexes are placed closest to their target sites on the XIST RNA. The linker regions among the domains are flexible, so the model here only represents the topology, but not the actual rigid shape. ‘m6A mod’ represents the m6A methylase complex and associated proteins. Figure adapted from Lu et al. [10].