HOXA11 silencing and endogenous HOXA11 antisense ribonucleic acid in the uterine endometrium
HOXA11 silencing and endogenous HOXA11 antisense ribonucleic acid in the uterine endometrium
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DOI：
10.1210/jc.87.6.2674
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发表时间：
2002-06-01
影响因子：
5.8
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Chau, YM;Pando, S;Taylor, HS
Hoxa11是胚胎子宫发育和成人子宫内膜周期发育的重要调节因子。靶向突变证明，Hoxa11是女性生育所必需的。在这里，我们展示了在成年小鼠和人类子宫内膜中存在的一个自然存在的Hoxa11(小鼠)/HOXA11(人)反义转录本。HOXA11反义转录水平在月经周期中变化，反义RNA水平峰值出现在增殖期中期，与mRNA表达水平成反比。HOXA11蛋白水平与峰值mRNA水平存在时间相关性。在原代培养的基质细胞中，孕酮下调HOXA11的反义转录，随后HOXA11的mRNA表达上调，提示反义转录可能在调节mRNA的表达中起作用。通过将Hoxa11反义寡核苷酸导入小鼠子宫来阻断Hoxa11功能的尝试失败了，这表明Hoxa11反义并不通过形成正义/反义双链来调节Hoxa11的mRNA。我们认为HOXA11反义通过转录干扰发挥作用，通过竞争COMM在基因上的转录来抑制HOXA11的表达，而不是通过正义/反义相互作用。
Hoxa11 is an essential regulator of embryonic uterine development and the cyclic development of the adult uterine endometrium. Hoxa11 is required for female fertility, as evidenced by targeted mutation. Here we demonstrate a naturally occurring Hoxa11 (mouse)/HOXA11 (human) antisense transcript present in the adult mouse and human endometrium. HOXA11 antisense transcript levels varied during the menstrual cycle, with peak antisense RNA levels occurring in the midproliferative phase, varying inversely with mRNA expression levels. HOXA11 protein levels correlated temporally with peak mRNA levels. In primary stromal cell culture, progesterone down-regulated HOXA11 antisense transcription, and this was followed by up-regulation of HOXA11 mRNA, suggesting a possible role for the antisense transcript in regulating mRNA expression. Attempts to block Hoxa11 function by transfection of the murine uterus with Hoxa11 antisense oligonucleotides failed to interrupt normal uterine function, suggesting that Hoxa11 antisense does not regulate Hoxa11 mRNA by formulation of sense/antisense duplexes. We propose that HOXA11 antisense functions by transcriptional interference, repressing HOXA11 expression by competing for transcription of the comm on gene, rather than by sense/antisense interaction.