The microRNA-processing enzyme Dicer is essential for thyroid function.

The microRNA-processing enzyme Dicer is essential for thyroid function.
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DOI:
10.1371/journal.pone.0027648
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Di Lauro R
Di Lauro R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Frezzetti D;Reale C;Calì G;Nitsch L;Fagman H;Nilsson O;Scarfò M;De Vita G;Di Lauro R

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Dicer是一种III型核糖核酸酶,是microRNA(miRNAs)生物合成所必需的,miRNAs是一类在转录后水平调节基因表达的小的非编码RNA。为了探索miRNA在甲状腺功能中的功能作用,我们产生了甲状腺细胞特异性Dicer条件性敲除小鼠。在这里,我们发现甲状腺的发育和早期分化不受Dicer缺乏的影响,而严重的甲状腺功能减退症在出生后逐渐发展,导致体重减轻和寿命缩短。基因敲除小鼠的组织学和分子特征揭示了甲状腺滤泡结构的急剧丧失,这与功能失常和几种分化标志物的下调有关。这项研究中提供的数据首次表明,完整的miRNAs加工机制对甲状腺生理学至关重要,这表明特定miRNAs的失调也可能参与人类甲状腺功能障碍。
Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.
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