Kanke Matt, Jambor Helena, Reich John, Marches Brittany, Gstir Ronald, Ryu Young Hee, Ephrussi Anne, Macdonald Paul M
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
RNA. 2015 Jun;21(6):1096-109. doi: 10.1261/rna.048298.114. Epub 2015 Apr 10.
The Drosophila oskar (osk) mRNA is unusual in that it has both coding and noncoding functions. As an mRNA, osk encodes a protein required for embryonic patterning and germ cell formation. Independent of that function, the absence of osk mRNA disrupts formation of the karyosome and blocks progression through oogenesis. Here we show that loss of osk mRNA also affects the distribution of regulatory proteins, relaxing their association with large RNPs within the germline, and allowing them to accumulate in the somatic follicle cells. This and other noncoding functions of the osk mRNA are mediated by multiple sequence elements with distinct roles. One role, provided by numerous binding sites in two distinct regions of the osk 3' UTR, is to sequester the translational regulator Bruno (Bru), which itself controls translation of osk mRNA. This defines a novel regulatory circuit, with Bru restricting the activity of osk, and osk in turn restricting the activity of Bru. Other functional elements, which do not bind Bru and are positioned close to the 3' end of the RNA, act in the oocyte and are essential. Despite the different roles played by the different types of elements contributing to RNA function, mutation of any leads to accumulation of the germline regulatory factors in the follicle cells.
果蝇的osk（oskar）mRNA不同寻常，因为它兼具编码和非编码功能。作为一种mRNA，osk编码胚胎模式形成和生殖细胞形成所需的一种蛋白质。不依赖于该功能，osk mRNA的缺失会破坏染色质核仁的形成并阻断卵子发生进程。我们在此表明，osk mRNA的缺失还会影响调控蛋白的分布，使其与生殖系内的大型核糖核蛋白体（RNP）的结合变松散，并使其在体细胞滤泡细胞中积累。osk mRNA的这一功能及其他非编码功能由具有不同作用的多个序列元件介导。osk 3'非翻译区（UTR）两个不同区域中的众多结合位点发挥的一个作用是隔离翻译调节因子布鲁诺（Bru），而布鲁诺本身控制着osk mRNA的翻译。这定义了一种新型调控回路，其中布鲁诺限制osk的活性，而osk反过来限制布鲁诺的活性。其他不与布鲁诺结合且位于RNA 3'端附近的功能元件在卵母细胞中起作用且必不可少。尽管不同类型的元件在RNA功能中发挥不同作用，但任何一个元件发生突变都会导致生殖系调控因子在滤泡细胞中积累。
