Loedige, Inga and Stotz, Mathias and Qamar, Saadia and Kramer, Katharina and Hennig, Janosch and Schubert, Thomas and Loeffler, Patrick and Laengst, Gernot and Merkl, Rainer and Urlaub, Henning and Meister, Gunter (2014) The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation. GENES & DEVELOPMENT, 28 (7). pp. 749-764. ISSN 0890-9369, 1549-5477
Full text not available from this repository. (Request a copy)Abstract
The Drosophila protein brain tumor (Brat) forms a complex with Pumilio (Pum) and Nanos (Nos) to repress hunchback (hb) mRNA translation at the posterior pole during early embryonic development. It is currently thought that complex formation is initiated by Pum, which directly binds the hb mRNA and subsequently recruits Nos and Brat. Here we report that, in addition to Pum, Brat also directly interacts with the hb mRNA. We identify Brat-binding sites distinct from the Pum consensus motif and show that RNA binding and translational repression by Brat do not require Pum, suggesting so far unrecognized Pum-independent Brat functions. Using various biochemical and biophysical methods, we also demonstrate that the NHL (NCL-1, HT2A, and LIN-41) domain of Brat, a domain previously believed to mediate protein-protein interactions, is a novel, sequence-specific ssRNA-binding domain. The Brat-NHL domain folds into a six-bladed beta propeller, and we identify its positively charged top surface as the RNA-binding site. Brat belongs to the functional diverse TRIM (tripartite motif)-NHL protein family. Using structural homology modeling, we predict that the NHL domains of all TRIM-NHL proteins have the potential to bind RNA, indicating that Brat is part of a conserved family of RNA-binding proteins.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SELF-RENEWAL; CELL-GROWTH; STEM-CELLS; DROSOPHILA; PROTEIN; PUMILIO; TUMOR; EXPRESSION; REVEALS; NANOS; BRAT; RNA binding; TRIM-NHL; gene regulation; hunchback; translational repression |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III > Prof. Dr. Gernot Längst |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Nov 2019 09:27 |
| Last Modified: | 15 Nov 2019 09:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10379 |
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