Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition.
Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition.
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DOI：
10.1186/s13059-015-0659-4
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发表时间：
2015-05-12
期刊：
影响因子：
12.3
通讯作者：
Smibert CA
中科院分区：
文献类型：
--
作者：
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;Smibert CA
脑肿瘤（Brain tumor，BRAT）是TRIM-NHL蛋白家族的果蝇成员。该家族在后生动物中是保守的，其成员作为转录后调节因子发挥作用。BRAT被认为是通过与RNA结合蛋白Pumilio（PUM）的相互作用间接募集到mRNA中。然而，最近已经证明BRAT直接与RNA结合。BRAT识别的精确序列、BRAT介导的调控程度以及PUM和BRAT在转录后调控中的确切作用尚不清楚。果蝇胚胎中与BRAT或PUM相关的转录物的全基因组鉴定表明，它们主要结合非重叠的mRNA组。BRAT结合编码与多种功能相关的蛋白质的mRNA，其中许多功能与由BRAT相关转录物实现的功能不同。体外和体内数据的计算分析确定了一种新的RNA基序识别的BRAT，赋予BRAT介导的组织培养细胞的调节。BRAT相关mRNA的调节状态表明BRAT在转录后调节中的重要作用，包括先前未鉴定的转录物降解作用。对缺乏功能性BRAT的胚胎的转录组学分析揭示了在母体-合子转变期间介导数百种母体mRNA衰变的重要作用。我们的研究结果代表了第一个全基因组分析的mRNA与TRIM-NHL蛋白和第一个识别的RNA基序结合这个蛋白质家族。BRAT是早期胚胎中一个重要的转录后调节因子，其作用机制在很大程度上独立于PUM。本文的在线版本（doi：10.1186/s13059-015-0659-4）包含补充材料，可供授权用户使用。
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. 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. 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. The online version of this article (doi:10.1186/s13059-015-0659-4) contains supplementary material, which is available to authorized users.
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