Ryder Sean P, Frater Leah A, Abramovitz Dana L, Goodwin Elizabeth B, Williamson James R
Department of Molecular Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, Mail Stop MB-33, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Struct Mol Biol. 2004 Jan;11(1):20-8. doi: 10.1038/nsmb706. Epub 2003 Dec 29.
The post-transcriptional regulation of gene expression underlies several critical developmental phenomena. In metazoa, gene products that are expressed, silenced and packaged during oogenesis govern early developmental processes prior to nascent transcription activation. Furthermore, tissue-specific alternative splicing of several transcription factors controls pattern formation and organ development. A highly conserved family of proteins containing a STAR/GSG RNA-binding domain is essential to both processes. Here, we identify the consensus STAR-binding element (SBE) required for specific mRNA recognition by GLD-1, a key regulator of Caenorhabditis elegans germline development. We have identified and verified new GLD-1 repression targets containing this sequence. The results suggest additional functions of GLD-1 in X-chromosome silencing and early embryogenesis. The SBE is present in Quaking and How mRNA targets, suggesting that STAR protein specificity is highly conserved. Similarities between the SBE and the branch-site signal indicate a possible competition mechanism for STAR/GSG regulation of splicing variants.
基因表达的转录后调控是多种关键发育现象的基础。在多细胞动物中，在卵子发生过程中表达、沉默和包装的基因产物在新生转录激活之前调控早期发育过程。此外，几种转录因子的组织特异性可变剪接控制着模式形成和器官发育。一个包含STAR/GSG RNA结合结构域的高度保守的蛋白质家族对这两个过程都至关重要。在这里，我们确定了秀丽隐杆线虫生殖系发育的关键调节因子GLD-1特异性识别mRNA所需的共有STAR结合元件（SBE）。我们已经鉴定并验证了含有该序列的新的GLD-1抑制靶点。结果表明GLD-1在X染色体沉默和早期胚胎发生中具有额外功能。SBE存在于Quaking和How mRNA靶点中，表明STAR蛋白特异性高度保守。SBE与分支位点信号之间的相似性表明了STAR/GSG对剪接变体调控的一种可能的竞争机制。
