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Cell Stem Cell:可变聚腺苷酸化可抵抗miRNA的调节

来源:生物谷 2012-03-02 12:06

在肌细胞生成过程中,Pax3是一个关键的调节子,它在激活的成体肌肉干细胞或卫星细胞(SCs,satellite cells)中短暂表达。Pax3也在QSCs(quiescent SCs)的一个亚群中表达,但只限于特定种类的肌肉细胞。近日,斯坦福大学等处的研究人员发现,Pax3的表达水平受miR-206的调节。相关论文发表在国际知名杂志Cell Stem Cell上。

在大多数的QSCs和激活的SCs中,miR-206的表达可抑制Pax3的表达。然而,高表达Pax3的QSCs中,miR-206也发生高水平的表达。在这些QSCs中,Pax3转录本易受可变腺苷酸化(alternative polyadenylation)加工,末端带上短的3'非翻译区(UTR),从而对miR-206的调节产生耐受。

出生后,Pax3在SCs激活过程中短暂表达,促进增殖,抑制分化。在随后的肌原性分化过程中,Pax3蛋白被单泛素化后经蛋白酶体降解,其RNA被至少两种microRNA降解。

研究结果表明,可变聚腺苷酸化在miRNA调节、干细胞功能和干细胞异质性等方面都有重要作用。(生物谷Bioon.com)

Alternative Polyadenylation Mediates MicroRNA Regulation of Muscle Stem Cell Function

Stéphane C. Boutet, Tom H. Cheung, Navaline L. Quach, Ling Liu, Sara L. Prescott, Abdolhossein Edalati, Kevin Iori, Thomas A. Rando

Pax3, a key myogenic regulator, is transiently expressed during activation of adult muscle stem cells, or satellite cells (SCs), and is also expressed in a subset of quiescent SCs (QSCs), but only in specific muscles. The mechanisms regulating these variations in expression are not well understood. Here we show that Pax3 levels are regulated by miR-206, a miRNA with a previously demonstrated role in myogenic differentiation. In most QSCs and activated SCs, miR-206 expression suppresses Pax3 expression. Paradoxically, QSCs that express high levels of Pax3 also express high levels of miR-206. In these QSCs, Pax3 transcripts are subject to alternative polyadenylation, resulting in transcripts with shorter 3′ untranslated regions (3′UTRs) that render them resistant to regulation by miR-206. Similar alternate polyadenylation of the Pax3 transcript also occurs in myogenic progenitors during development. Our findings may reflect a general role of alternative polyadenylation in circumventing miRNA-mediated regulation of stem cell function.

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