A template for RNA assembly
Researchers using the NE-CAT 24-ID-C beamline at the APS are developing a clearer picture of RNA function and assembly mechanisms.
It is becoming increasingly clear that most cellular processes involve the coordinated action of large RNA molecules, many of which adopt complex tertiary structures. As interest in RNA function and RNA nanotechnology grows, it is essential to expand our understanding of RNA assembly mechanisms.
Although there is no single model for RNA architectural assembly, several major themes have emerged. One of the earliest models involves rapid collapse to a stable, but kinetically trapped, RNA structure that requires subsequent rearrangement by chaperone proteins to adopt the active native state (chaperone-dependent remodeling).
Although the importance of large noncoding RNAs is increasingly appreciated, our understanding of their structures and architectural dynamics remains limited. In particular, we know little about RNA folding intermediates and how they facilitate the productive assembly of RNA tertiary structures. Here, we report the crystal structure of an obligate intermediate that is required during the earliest stages of group II intron folding.
Composed of domain 1 from the Oceanobacillus iheyensis group II intron (266 nucleotides), this intermediate retains native-like features but adopts a compact conformation in which the active site cleft is closed. Transition between this closed and the open (native) conformation is achieved through discrete rotations of hinge motifs in two regions of the molecule. The open state is then stabilized by sequential docking of downstream intron domains, suggesting a ‘first come, first folded’ strategy that may represent a generalizable pathway for assembly of large RNA and ribonucleoprotein structures.
Chen Zhao, Kanagalaghatta R Rajashankar, Marco Marcia and Anna Marie Pyle, “Crystal structure of group II intron domain 1 reveals a template for RNA assembly,” Nature Chemical Biology, Article (2015), DOI: 10.1038/nchembio.1949, Published Online October 26, 2015.