Structural and Biochemical Studies of the RNA-Associated Sm Protein Superfamily

Abstract

Sm proteins comprise a broad, evolutionarily conserved family that plays key roles in RNA processing, in organisms ranging from bacteria to human. Eukaryotic Sm proteins form snRNP cores and help organize the RNA splicing machinery, while bacterial Sm proteins (Hfq) interact with small noncoding RNAs to regulate quorum sensing and other sRNA-based pathways; the existence of Sm-like proteins in the Archaea suggests the importance of this ancient family in the early evolution of RNA processing. To decipher the intricate structure ↔ function ↔ evolution relationships in this family, we are pursuing three lines of work that encompass computational analysis and experimental discovery: (i) development of a quantitative ‘definition’ of the Sm fold, enabling structural analyses and comparison to other small nucleic acid-binding folds, as well as molecular dynamics simulations of Sm proteins; (ii) discovery and identification of small noncoding RNAs bound in vivo by Sm homologs from deep-branching phyla; (iii) crystallographic studies of archaeal Sm proteins and assemblies. Recent results from these directions will be presented.