Anderson Bart R, Chopra Pankaj, Suhl Joshua A, Warren Stephen T, Bassell Gary J
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nucleic Acids Res. 2016 Aug 19;44(14):6649-59. doi: 10.1093/nar/gkw593. Epub 2016 Jul 4.
Fragile X mental retardation protein (FMRP) is a multifunctional RNA-binding protein with crucial roles in neuronal development and function. Efforts aimed at elucidating how FMRP target mRNAs are selected have produced divergent sets of target mRNA and putative FMRP-bound motifs, and a clear understanding of FMRP's binding determinants has been lacking. To clarify FMRP's binding to its target mRNAs, we produced a shared dataset of FMRP consensus binding sequences (FCBS), which were reproducibly identified in two published FMRP CLIP sequencing datasets. This comparative dataset revealed that of the various sequence and structural motifs that have been proposed to specify FMRP binding, the short sequence motifs TGGA and GAC were corroborated, and a novel TAY motif was identified. In addition, the distribution of the FCBS set demonstrates that FMRP preferentially binds to the coding region of its targets but also revealed binding along 3' UTRs in a subset of target mRNAs. Beyond probing these putative motifs, the FCBS dataset of reproducibly identified FMRP binding sites is a valuable tool for investigating FMRP targets and function.
脆性X智力低下蛋白（FMRP）是一种多功能RNA结合蛋白，在神经元发育和功能中起关键作用。旨在阐明FMRP如何选择靶mRNA的研究产生了不同的靶mRNA集和假定的FMRP结合基序，并且一直缺乏对FMRP结合决定因素的清晰理解。为了阐明FMRP与其靶mRNA的结合，我们生成了一个FMRP共有结合序列（FCBS）的共享数据集，该数据集在两个已发表的FMRP CLIP测序数据集中被重复鉴定。这个比较数据集表明，在已提出的用于指定FMRP结合的各种序列和结构基序中，短序列基序TGGA和GAC得到了证实，并且鉴定出了一个新的TAY基序。此外，FCBS集的分布表明FMRP优先与其靶标的编码区结合，但也揭示了在一部分靶mRNA的3' UTR上存在结合。除了探究这些假定基序之外，可重复鉴定的FMRP结合位点FCBS数据集是研究FMRP靶标和功能的宝贵工具。
