Unknown

Dataset Information

0

Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.


ABSTRACT: The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function.

SUBMITTER: Bhandari D 

PROVIDER: S-EPMC4003280 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.

Bhandari Dipankar D   Raisch Tobias T   Weichenrieder Oliver O   Jonas Stefanie S   Izaurralde Elisa E  

Genes & development 20140401 8


The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 thro  ...[more]

Similar Datasets

| S-EPMC5207322 | biostudies-literature
| S-EPMC4811204 | biostudies-literature
| S-EPMC6771390 | biostudies-literature
| S-EPMC3885283 | biostudies-literature
| S-EPMC3808610 | biostudies-literature
| S-EPMC1847662 | biostudies-literature
| S-EPMC5471237 | biostudies-literature
| S-EPMC5322899 | biostudies-literature
| S-EPMC3746937 | biostudies-literature
| S-EPMC9931213 | biostudies-literature