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Distinct modes of recruitment of the CCR 4– NOT complex by Drosophila and vertebrate Nanos
Author(s) -
Raisch Tobias,
Bhandari Dipankar,
Sabath Kevin,
Helms Sigrun,
Valkov Eugene,
Weichenrieder Oliver,
Izaurralde Elisa
Publication year - 2016
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.201593634
Subject(s) - biology , drosophila (subgenus) , vertebrate , microbiology and biotechnology , evolutionary biology , genetics , gene
Abstract Nanos proteins repress the expression of target mRNA s by recruiting effector complexes through non‐conserved N‐terminal regions. In vertebrates, Nanos proteins interact with the NOT 1 subunit of the CCR 4– NOT effector complex through a NOT 1 interacting motif ( NIM ), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR 4– NOT deadenylase complex in invertebrates. Here, we identify an effector domain ( NED ) that is necessary for the Drosophila melanogaster ( Dm ) Nanos to repress mRNA targets. The NED recruits the CCR 4– NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C‐terminal domains of NOT 1–3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT 1 and NOT 3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N‐terminal regions of Nanos proteins recruit CCR 4– NOT to assemble analogous repressive complexes.