abd-A regulation by the iab-8 noncoding RNA.
abd-A regulation by the iab-8 noncoding RNA.
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DOI：
10.1371/journal.pgen.1002720
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Bender W
中科院分区：
文献类型：
--
作者：
Gummalla M;Maeda RK;Castro Alvarez JJ;Gyurkovics H;Singari S;Edwards KA;Karch F;Bender W
黑腹果蝇的同源异型基因在染色体上按照它们影响的身体部分的顺序排列。影响较后节的基因抑制较前节的基因。这种后验优势规则必须在腹部-A（abd-A）被腹部-B（abd-B）抑制的情况下加以限定。缺乏Abd-B的动物显示abd-A在第八腹节的表皮中异位表达，但不在中枢神经系统中表达。这些神经元细胞中的抑制是由92 kb的非编码RNA完成的。这种“iab-8 RNA”产生一种微RNA来抑制abd-A，但也有第二种冗余的抑制机制，只在“顺式”中起作用。abd-A启动子的转录干扰是最可能的机制。虽然在许多生物体中发现了长的非编码RNA，但很难确定它们的分子功能。果蝇（Drosophila melanogaster）中的同源异型基因簇含有许多这样的非编码RNA。我们已经确定了一个这样的非编码RNA，一个92 kb的转录单位，从双胸复合体。这种转录物称为iab-8 ncRNA，与同源异型转录因子Abdominal-B一起沿着在第八腹节的中枢神经系统细胞中产生。另一种同源异型转录因子abdominal-A在这些细胞中受到抑制。一般认为这些细胞中的abdominal-A抑制是由Abdominal-B蛋白介导的。然而，在这里，我们表明，它不是抑制abdominal-A的Abdominal-B，但iab-8 ncRNA。这种抑制是通过两种冗余机制完成的; iab-8前体产生一种靶向abdominal-A mRNA的微小RNA，而iab-8转录干扰abdominal-A启动子，后者位于iab-8 ncRNA poly（A）位点的下游。
The homeotic genes in Drosophila melanogaster are aligned on the chromosome in the order of the body segments that they affect. The genes affecting the more posterior segments repress the more anterior genes. This posterior dominance rule must be qualified in the case of abdominal-A (abd-A) repression by Abdominal-B (Abd-B). Animals lacking Abd-B show ectopic expression of abd-A in the epidermis of the eighth abdominal segment, but not in the central nervous system. Repression in these neuronal cells is accomplished by a 92 kb noncoding RNA. This “iab-8 RNA” produces a micro RNA to repress abd-A, but also has a second, redundant repression mechanism that acts only “in cis.” Transcriptional interference with the abd-A promoter is the most likely mechanism. Although long, noncoding RNAs have been found in many organisms, it has been difficult to assign to them any molecular function. The homeotic gene clusters in the fruit fly, Drosophila melanogaster, contain many such noncoding RNAs. We have characterized one such noncoding RNA, a 92 kb transcription unit from within the bithorax complex. This transcript, called the iab-8 ncRNA, is made in the cells of the central nervous system in the eighth abdominal segment, along with the homeotic transcription factor Abdominal-B. Another homeotic transcription factor, abdominal-A, is repressed in these cells. It has generally been assumed that abdominal-A repression in these cells is mediated by the Abdominal-B protein. However, here we show that it is not Abdominal-B that represses abdominal-A, but the iab-8 ncRNA. This repression is accomplished by two redundant mechanisms; the iab-8 precursor produces a micro RNA, which targets the abdominal-A mRNA, and iab-8 transcription interferes with the abdominal-A promoter, which lies just downstream of the iab-8 ncRNA poly(A) site.
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