在肌細(xì)胞生成過程中,，Pax3是一個(gè)關(guān)鍵的調(diào)節(jié)子，它在激活的成體肌肉干細(xì)胞或衛(wèi)星細(xì)胞（SCs,satellite cells）中短暫表達(dá),。Pax3也在QSCs（quiescent SCs）的一個(gè)亞群中表達(dá),，但只限于特定種類的肌肉細(xì)胞。近日,，斯坦福大學(xué)等處的研究人員發(fā)現(xiàn),，Pax3的表達(dá)水平受miR-206的調(diào)節(jié)。相關(guān)論文發(fā)表在國際知名雜志Cell Stem Cell上,。
在大多數(shù)的QSCs和激活的SCs中,，miR-206的表達(dá)可抑制Pax3的表達(dá)。然而,，高表達(dá)Pax3的QSCs中,，miR-206也發(fā)生高水平的表達(dá)。在這些QSCs中,，Pax3轉(zhuǎn)錄本易受可變腺苷酸化（alternative polyadenylation）加工,，末端帶上短的3'非翻譯區(qū)（UTR），從而對miR-206的調(diào)節(jié)產(chǎn)生耐受,。
出生后，Pax3在SCs激活過程中短暫表達(dá),，促進(jìn)增殖,，抑制分化。在隨后的肌原性分化過程中,，Pax3蛋白被單泛素化后經(jīng)蛋白酶體降解,，其RNA被至少兩種microRNA降解。
研究結(jié)果表明,，可變聚腺苷酸化在miRNA調(diào)節(jié),、干細(xì)胞功能和干細(xì)胞異質(zhì)性等方面都有重要作用,。（生物谷Bioon.com）
doi:10.1016/j.stem.2012.01.017
PMC:
PMID:
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.
