N-6-methyladenosine (m(6)A) "readers" play an important role in mRNA functions and metabolism. YTHDC2, as one of the m(6)A readers, controls fertileness through decreasing associated mRNA abundance and enhancing the translation efficiency of related mRNA via binding the targeted m(6)A RNA. However, how YTH domain of YTHDC2 recognize m(6)A RNA is still unknown. In this study, we determined the crystal structure of human YTHDC2 YTH domain, which adopts similar architecture to other solved YTH domain structures. YTHDC2 contains a conserved m(6)A binding pocket, and similar RNA binding surface shared by YTHDCI. (C) 2019 Elsevier Inc. All rights reserved.