Spliceosome activation: U4 is the path, stem I is the goal, and Prp8 is the keeper. Let's cheer for the ATPase Brr2!

During pre-mRNA splicing, the spliceosome is activated for catalysis by unwinding base-paired U4/U6 small nuclear RNAs, a step that must be precisely timed. We know that unwinding requires the ATPase Brr2, but the mechanism and regulation of unwinding have been understood poorly. In the November 1, 2012, issue of Genes & Development, Hahn and colleagues (pp. 2408-2421) and Mozaffari-Jovin and colleagues (pp. 2422-2434) defined a pathway for U4/U6 unwinding. Moreover, Mozaffari-Jovin and colleagues suggested a mechanism for regulating Brr2.