Gruber Joshua J, Zatechka D Steven, Sabin Leah R, Yong Jeongsik, Lum Julian J, Kong Mei, Zong Wei-Xing, Zhang Zhenxi, Lau Chi-Kong, Rawlings Jason, Cherry Sara, Ihle James N, Dreyfuss Gideon, Thompson Craig B
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell. 2009 Jul 23;138(2):328-39. doi: 10.1016/j.cell.2009.04.046.
Here we identify a component of the nuclear RNA cap-binding complex (CBC), Ars2, that is important for miRNA biogenesis and critical for cell proliferation. Unlike other components of the CBC, Ars2 expression is linked to the proliferative state of the cell. Deletion of Ars2 is developmentally lethal, and deletion in adult mice led to bone marrow failure whereas parenchymal organs composed of nonproliferating cells were unaffected. Depletion of Ars2 or CBP80 from proliferating cells impaired miRNA-mediated repression and led to alterations in primary miRNA processing in the nucleus. Ars2 depletion also reduced the levels of several miRNAs, including miR-21, let-7, and miR-155, that are implicated in cellular transformation. These findings provide evidence for a role for Ars2 in RNA interference regulation during cell proliferation.
在此，我们鉴定出核RNA帽结合复合体（CBC）的一个组分Ars2，它对miRNA生物合成很重要且对细胞增殖至关重要。与CBC的其他组分不同，Ars2的表达与细胞的增殖状态相关。Ars2的缺失在发育上是致死的，成年小鼠中Ars2的缺失导致骨髓衰竭，而由非增殖细胞组成的实质器官未受影响。从增殖细胞中去除Ars2或CBP80会损害miRNA介导的抑制作用，并导致细胞核中初级miRNA加工的改变。Ars2的缺失还降低了几种与细胞转化有关的miRNA的水平，包括miR-21、let-7和miR-155。这些发现为Ars2在细胞增殖过程中的RNA干扰调节作用提供了证据。
