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Molecular architecture of LSM 14 interactions involved in the assembly of mRNA silencing complexes
Author(s) -
Brandmann Tobias,
Fakim Hana,
Padamsi Zoya,
Youn JiYoung,
Gingras AnneClaude,
Fabian Marc R,
Jinek Martin
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797869
Subject(s) - biology , gene silencing , messenger rna , microbiology and biotechnology , genetics , gene
The LSM domain‐containing protein LSM 14/Rap55 plays a role in mRNA decapping, translational repression, and RNA granule (P‐body) assembly. How LSM 14 interacts with the mRNA silencing machinery, including the eIF 4E‐binding protein 4E‐T and the DEAD ‐box helicase DDX 6, is poorly understood. Here we report the crystal structure of the LSM domain of LSM 14 bound to a highly conserved C‐terminal fragment of 4E‐T. The 4E‐T C‐terminus forms a bi‐partite motif that wraps around the N‐terminal LSM domain of LSM 14. We also determined the crystal structure of LSM 14 bound to the C‐terminal RecA‐like domain of DDX 6. LSM 14 binds DDX 6 via a unique non‐contiguous motif with distinct directionality as compared to other DDX 6‐interacting proteins. Together with mutational and proteomic studies, the LSM 14‐ DDX 6 structure reveals that LSM 14 has adopted a divergent mode of binding DDX 6 in order to support the formation of mRNA silencing complexes and P‐body assembly.