A Divergent Sm Fold in EDC3 Proteins Mediates DCP1 Binding and P-Body Targeting

Abstract

Members of the (L)Sm (Sm and Sm-like) protein family are found across all kingdoms of life and play crucial roles in RNA metabolism. The P-body component EDC3 (enhancer of decapping 3) is a divergent member of this family that functions in mRNA decapping. EDC3 is composed of a N-terminal LSm domain, a central FDF domain, and a C-terminal YjeF-N domain. We show that this modular architecture enables EDC3 to interact with multiple components of the decapping machinery, including DCP1, DCP2, and Me31B. The LSm domain mediates DCP1 binding and P-body localization. We determined the three-dimensional structures of the LSm domains of Drosophila melanogaster and human EDC3 and show that the domain adopts a divergent Sm fold that lacks the characteristic N-terminal α-helix and has a disrupted β4-strand. This domain remains monomeric in solution and lacks several features that canonical (L)Sm domains require for binding RNA. The structures also revealed a conserved patch of surface residues that are required for the interaction with DCP1 but not for P-body localization. The conservation of surface and of critical structural residues indicates that LSm domains in EDC3 proteins adopt a similar fold that has separable novel functions that are absent in canonical (L)Sm proteins.

SUPPLEMENTAL MATERIAL

We are grateful to Horst Kessler and the staff of the Bavarian NMR Centre at the Technical University, Munich, for access to spectrometers and technical support. We thank Thilo Stehle and Christoph Schall for access to the rotating anode used to prescreen crystals and Kornelius Zeth for helpful discussions.

This study was supported by the Max Planck Society, and the Human Frontier Science Program Organization (HFSPO). A.E. is the recipient of a fellowship from the Portuguese Foundation for Science and Technology. O.W. holds a personal VIDI fellowship from the Dutch National Science Organization (NWO-VIDI, CW 700.54.427).