BackgroundBrain 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.ResultsGenome-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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0659-4) contains supplementary material, which is available to authorized users.
We developed an assay to quantify LDL transcytosis across endothelial cells and discovered an unexpected role for SR-BI. Elucidating the mechanisms of LDL transcytosis may identify novel targets for the prevention or therapy of atherosclerosis.
This study examines the experiences of fathers of children diagnosed with cancer. In this grounded theory study, participating fathers were qualitatively interviewed using a theoretical sampling approach. Results indicate fathers to be profoundly affected by their child's condition of cancer. Fathers' experiences include isolation and heightened sadness and uncertainty. Paternal roles comprise providing family support, sufficient resources, and seeking to maintain family stabilization. Post-diagnosis lived experience is described to hold new meaning as fathers reconcile the presence of childhood cancer within the life of their child and family. Strategies of resistance are demonstrated as fathers combat the devastating impacts of cancer through a commitment to family integration, healthy personal lifestyle and attitudes, support seeking, spirituality, and reframing of priorities. An emerging model is presented, as are implications for practice and recommendations.
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