1. Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition.
- Author
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Laver JD, Li X, Ray D, Cook KB, Hahn NA, Nabeel-Shah S, Kekis M, Luo H, Marsolais AJ, Fung KY, Hughes TR, Westwood JT, Sidhu SS, Morris Q, Lipshitz HD, and Smibert CA
- Subjects
- Animals, Binding Sites, Brain Neoplasms diagnosis, DNA-Binding Proteins metabolism, Drosophila embryology, Drosophila Proteins metabolism, Epigenetic Repression, Female, Gene Expression Regulation, Developmental, Genetic Association Studies, Mutation, Nuclear Proteins, RNA, Messenger, Stored metabolism, RNA-Binding Proteins metabolism, Tissue Culture Techniques, Transcription Factors genetics, Transcription Factors metabolism, Brain Neoplasms genetics, DNA-Binding Proteins genetics, Drosophila genetics, Drosophila Proteins genetics, RNA, Messenger, Stored genetics, RNA-Binding Proteins genetics
- Abstract
Background: Brain tumor (BRAT) is a Drosophila member of the TRIM-NHL protein family. This family is conserved among metazoans and its members function as post-transcriptional regulators. BRAT was thought to be recruited to mRNAs indirectly through interaction with the RNA-binding protein Pumilio (PUM). However, it has recently been demonstrated that BRAT directly binds to RNA. The precise sequence recognized by BRAT, the extent of BRAT-mediated regulation, and the exact roles of PUM and BRAT in post-transcriptional regulation are unknown., Results: Genome-wide identification of transcripts associated with BRAT or with PUM in Drosophila embryos shows that they bind largely non-overlapping sets of mRNAs. BRAT binds mRNAs that encode proteins associated with a variety of functions, many of which are distinct from those implemented by PUM-associated transcripts. Computational analysis of in vitro and in vivo data identified a novel RNA motif recognized by BRAT that confers BRAT-mediated regulation in tissue culture cells. The regulatory status of BRAT-associated mRNAs suggests a prominent role for BRAT in post-transcriptional regulation, including a previously unidentified role in transcript degradation. Transcriptomic analysis of embryos lacking functional BRAT reveals an important role in mediating the decay of hundreds of maternal mRNAs during the maternal-to-zygotic transition., Conclusions: Our results represent the first genome-wide analysis of the mRNAs associated with a TRIM-NHL protein and the first identification of an RNA motif bound by this protein family. BRAT is a prominent post-transcriptional regulator in the early embryo through mechanisms that are largely independent of PUM.
- Published
- 2015
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