Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0355, USA.
G3 (Bethesda). 2022 Jan 4;12(1). doi: 10.1093/g3journal/jkab374.
Long noncoding RNAs (lncRNAs) have been implicated in a variety of processes in development, differentiation, and disease. In Drosophila melanogaster, the bithorax Hox cluster contains three Hox genes [Ultrabithorax (Ubx), abdominal-A, and Abdominal-B], along with a number of lncRNAs, most with unknown functions. Here, we investigated the function of a lncRNA, lncRNA:PS4 that originates in the second intron of Ubx and is transcribed in the antisense orientation to Ubx. The expression pattern of lncRNA:PS4 is complementary to Ubx in the thoracic primordia, and the lncRNA:PS4 coding region overlaps the location of the large insertion that causes the dominant homeotic mutation Contrabithorax-1 (UbxCbx-1), which partially transforms Drosophila wings into halteres via ectopic activation of Ubx. This led us to investigate the potential role of this lncRNA in regulation of Ubx expression. The UbxCbx-1 mutation dramatically changes the pattern of lncRNA:PS4, eliminating the expression of most lncRNA:PS4 sequences from parasegment 4 (where Ubx protein is normally absent) and ectopically activating lncRNA:PS4 at high levels in the abdomen (where Ubx is normally expressed). These changes, however, did not lead to changes in the Ubx embryonic transcription pattern. Targeted deletion of the two promoters of lncRNA:PS4 did not result in the change of Ubx expression in the embryos. In the genetic background of a UbxCbx-1 mutation, the lncRNA:PS4 mutation does slightly enhance the ectopic activation of Ubx protein expression in wing discs and also slightly enhances the wing phenotype seen in UbxCbx-1 heterozygotes.
长链非编码 RNA(lncRNA)参与了发育、分化和疾病等多种过程。在黑腹果蝇中,双胸 Hox 簇包含三个 Hox 基因[Ultrabithorax(Ubx)、腹部-A 和腹部-B],以及许多 lncRNA,其中大多数具有未知功能。在这里,我们研究了 lncRNA:PS4 的功能,它起源于 Ubx 的第二个内含子,以 Ubx 的反义方向转录。lncRNA:PS4 的表达模式与胸部原基中的 Ubx 互补,而 lncRNA:PS4 编码区与导致显性同源突变 Contrabithorax-1(UbxCbx-1)的大片段插入重叠,该突变通过异位激活 Ubx 部分将果蝇翅膀转化为平衡棒。这导致我们研究了这种 lncRNA 在 Ubx 表达调控中的潜在作用。UbxCbx-1 突变极大地改变了 lncRNA:PS4 的表达模式,从旁节段 4(Ubx 蛋白通常不存在的地方)消除了大多数 lncRNA:PS4 序列的表达,并在腹部(Ubx 通常表达的地方)高水平异位激活 lncRNA:PS4。然而,这些变化并没有导致 Ubx 胚胎转录模式的改变。靶向删除 lncRNA:PS4 的两个启动子并没有导致胚胎中 Ubx 表达的变化。在 UbxCbx-1 突变的遗传背景下,lncRNA:PS4 突变略微增强了 Ubx 蛋白在翅膀盘上的异位激活表达,也略微增强了 UbxCbx-1 杂合子中观察到的翅膀表型。