Structural highlights
Function
BRAT_DROME Plays a central role in translation repression of hb mRNA by being recruited by nos and pum to the Nanos Response Element (NRE), a 16 bp sequence in the hb mRNA 3'-UTR. Probably recruited by other proteins to repress translation of other mRNAs in other tissues. Involved in the regulation of ribosomal RNA synthesis and cell growth. Participates in abdominal segmentation and imaginal disk development. Involved in brain tumor suppression, by acting as a growth suppressor in the larval brain.[1] [2]
Publication Abstract from PubMed
TRIM-NHL proteins are conserved among metazoans and control cell fate decisions in various stem cell linages. The Drosophila TRIM-NHL protein Brain tumor (Brat) directs differentiation of neuronal stem cells by suppressing self-renewal factors. Brat is an RNA-binding protein and functions as a translational repressor. However, it is unknown which RNAs Brat regulates and how RNA-binding specificity is achieved. Using RNA immunoprecipitation and RNAcompete, we identify Brat-bound mRNAs in Drosophila embryos and define consensus binding motifs for Brat as well as a number of additional TRIM-NHL proteins, indicating that TRIM-NHL proteins are conserved, sequence-specific RNA-binding proteins. We demonstrate that Brat-mediated repression and direct RNA-binding depend on the identified motif and show that binding of the localization factor Miranda to the Brat-NHL domain inhibits Brat activity. Finally, to unravel the sequence specificity of the NHL domain, we crystallize the Brat-NHL domain in complex with RNA and present a high-resolution protein-RNA structure of this fold.
The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation.,Loedige I, Jakob L, Treiber T, Ray D, Stotz M, Treiber N, Hennig J, Cook KB, Morris Q, Hughes TR, Engelmann JC, Krahn MP, Meister G Cell Rep. 2015 Nov 10;13(6):1206-20. doi: 10.1016/j.celrep.2015.09.068. Epub 2015, Oct 29. PMID:26527002[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sonoda J, Wharton RP. Drosophila Brain Tumor is a translational repressor. Genes Dev. 2001 Mar 15;15(6):762-73. PMID:11274060 doi:http://dx.doi.org/10.1101/gad.870801
- ↑ Frank DJ, Edgar BA, Roth MB. The Drosophila melanogaster gene brain tumor negatively regulates cell growth and ribosomal RNA synthesis. Development. 2002 Jan;129(2):399-407. PMID:11807032
- ↑ Loedige I, Jakob L, Treiber T, Ray D, Stotz M, Treiber N, Hennig J, Cook KB, Morris Q, Hughes TR, Engelmann JC, Krahn MP, Meister G. The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation. Cell Rep. 2015 Nov 10;13(6):1206-20. doi: 10.1016/j.celrep.2015.09.068. Epub 2015, Oct 29. PMID:26527002 doi:http://dx.doi.org/10.1016/j.celrep.2015.09.068
