| Description: | [DBS Seminar] Dipankar Bhandari (Department of Biochemistry, Max Planck Institute for Developmental Biology, Tuebingen, Germany) -- Nanos family RNA binding proteins recruit the CCR4-NOT complex to repress translation of their target mRNAs |
| Date: | Wednesday, Jan 13, 2016 |
| Time: | 4 p.m. - 5 p.m. |
| Venue: | 108, Lecture Hall Complex |
| Details: | The RNA-binding proteins of the Nanos family are conserved post-transcriptional mRNA regulators implicated in embryonic development and germ line stem cell maintenance in metazoans. They regulate the expression of target mRNAs by recruiting effector complexes, which include the CCR4-NOT deadenylase complex. Our work demonstrates that three human Nanos paralogs (Nanos1–3) interact with the NOT1 subunit of the CCR4-NOT complex through a 17 residues short linear motif which we termed NOT1-interacting motif (NIM) that is necessary and sufficient for Nanos-mediated translation repression1. Interestingly, single Drosophila melanogaster (Dm) Nanos ortholog lacks a detectable NIM motif. In the absence of the NIM motif it has remained unclear whether Dm Nanos recruits CCR4-NOT complex directly or relies on the interaction with additional partners for activity. We also identify an effector domain (NED), which is necessary and sufficient for the Dm Nanos to repress mRNA targets2. The NED recruits the CCR4–NOT complex through multiple binding sites, including a central peptide that interacts with the NOT1 and NOT3 subunits. Finally we show that the Dm NED and human NIM are interchangeable and perform analogous functions but have evolved different modes to interact with the CCR4-NOT complex. Our data reveal that Nanos proteins have maintained the ability to interact with the same partners to assemble similar repressive complexes using rapidly evolving sequence motifs. More generally, it provides a paradigm for the evolution of short linear motifs in disordered protein regions and illustrates how function can be preserved in the absence of sequence conservation. |
| Calendar: | Seminar Calendar (entered by psray) |