韓國首爾國立大學(xué)生物科學(xué)與創(chuàng)新性研究中心的科學(xué)家在microRNA自我調(diào)節(jié)功能的研究上取得最新的進展，相關(guān)成果文章發(fā)表在最新的Cell雜志上,。
microRNA是調(diào)節(jié)細(xì)胞功能的關(guān)鍵因子,，除了對細(xì)胞功能有重要的調(diào)節(jié)作用外，microRNA自身也需要被嚴(yán)格地調(diào)控,，方能發(fā)揮應(yīng)有的作用,。Lin28，一種多功能因子,，被報道具有下調(diào)let-7 miRNA的功能,，Lin28介導(dǎo)Let-7前體的末端尿苷化，從而阻斷了Dicer的處理過程及l(fā)et-7的成熟,。
但是這個過程的分子機制目前尚不清楚,。在本研究中，作者通過RNA親和純化和免疫共沉淀這些普通的實驗室技術(shù),， 闡明了一種不常見的Poly(A)多聚酶-TUT4,，該酶在Lin-28的參與下，結(jié)合到pre-let-7尚而阻斷其成熟,。
體外試驗發(fā)現(xiàn),，TUT4在Lin28幫助下，可以對pre-let-7進行尿苷化,。敲除了TUT4的鼠胚胎干細(xì)胞let-7表達水平上升,，最終失去了多能性。作者發(fā)現(xiàn)這種交互作用發(fā)生于GGAG基序,，該基序存在于pre-let-7的環(huán)部,。其它帶有此基序的miRNA前體，也可經(jīng)Lin28/TUT4途徑而得以尿苷化,。
這一研究結(jié)果,，對干細(xì)胞和癌癥生物學(xué)研究有很重要的意義。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 138, Issue 4, 696-708, 21 August 2009 doi:10.1016/j.cell.2009.08.002
TUT4 in Concert with Lin28 Suppresses MicroRNA Biogenesis through Pre-MicroRNA Uridylation
Inha Heo1, 2, Chirlmin Joo1, 2, Young-Kook Kim1, 2, Minju Ha1, Mi-Jeong Yoon1, Jun Cho1, Kyu-Hyeon Yeom1, Jinju Han1 and V. Narry Kim1, ,
1 Creative Research Center and School of Biological Sciences, Seoul National University, Seoul, Korea 151-742
As key regulators in cellular functions, microRNAs (miRNAs) themselves need to be tightly controlled. Lin28, a pluripotency factor, was reported to downregulate let-7 miRNA by inducing uridylation of let-7 precursor (pre-let-7). But the enzyme responsible for the uridylation remained unknown. Here we identify a noncanonical poly (A) polymerase, TUTase4 (TUT4), as the uridylyl transferase for pre-let-7. Lin28 recruits TUT4 to pre-let-7 by recognizing a tetra-nucleotide sequence motif (GGAG) in the terminal loop. TUT4 in turn adds an oligouridine tail to the pre-let-7, which blocks Dicer processing. Other miRNAs with the same sequence motif (miR-107, -143, and -200c) are regulated through the same mechanism. Knockdown of TUT4 and Lin28 reduces the level of stem cell markers, suggesting that they are required for stem cell maintenance. This study uncovers the role of TUT4 and Lin28 as specific suppressors of miRNA biogenesis, which has implications for stem cell research and cancer biology.
