p53肿瘤抑制因子是一种具有很多生长抑制目标的众所周知的转录激活因子。p53功能的破坏在多数癌症的发展过程中是一个根本性事件。微RNA（miRNA）已成为肿瘤抑制中的重要因子，在这项研究工作中，p53 和miRNA之间一个出乎意料的联系被发现。
在一个独立于它在调控转录中所扮演角色的相互作用中，作为对DNA损伤的反应，p53增强几种生长抑制性miRNA的转录后成熟过程，其中包括miR-16-1、miR-143和miR-145。这表明，p53调控miRNA生物生成的能力可能会有助于提高其致癌潜力。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 460, 529-533 (23 July 2009) | doi:10.1038/nature08199
Modulation of microRNA processing by p53
Hiroshi I. Suzuki1, Kaoru Yamagata2,3, Koichi Sugimoto4, Takashi Iwamoto5, Shigeaki Kato2,3 & Kohei Miyazono1
1 Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2 Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
3 ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan
4 Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
5 The Center for Education in Laboratory Animal Research and Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan
6 Correspondence to: Kohei Miyazono1 Correspondence and requests for materials should be addressed to K.M.
MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development1, a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis2, 3, 4. This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. In HCT116 cells and human diploid fibroblasts, p53 interacts with the Drosha processing complex through the association with DEAD-box RNA helicase p68 (also known as DDX5) and facilitates the processing of primary miRNAs to precursor miRNAs. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between Drosha complex and p68, leading to attenuation of miRNA processing activity. These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.
