Roquin mediates mRNA degradation by recognizing the constitutive-decay element
(CDE) in the 3' untranslated region of the target gene followed by recruitment
of the deadenylation machinery. Deficiency or dysfunction of Roquin has been
associated with autoimmunity and inflammation. To establish the structural basis
for the recognition of CDE RNA by Roquin, the crystal structure of the ROQ
domain of human Roquin-2 was determined in ligand-free and CDE-derived RNA-bound
forms. The ROQ domain of Roquin-2 folded into a winged-helix structure in which
the wing region showed structural flexibility and acted as a lid for RNA
binding. The CDE RNA, forming a stem-loop structure, bound to the positively
charged surface of the ROQ domain and was mainly recognized via direct
interactions with the phosphate backbone in the 5' half of the stem-loop and its
triloop and via indirect water-mediated interactions. Structural comparison with
Roquin-1 revealed conserved features of the RNA-binding mode. Therefore, it is
suggested that the Roquin proteins function redundantly in mRNA degradation.
