青年学者Nature解析miRNA对 p53的关键调控

　　

生物通报道，来自日本京都大学医学院的科学家在最新一期的Nature杂志上发表microRNA与p53的最新研究进展Modulation of microRNA processing by p53。

 

一直以来p53是科学家研究的热点抑癌基因，p53蛋白可控制多数转录激活因子，因此备受关注。microRNA也是癌症调控研究的热点课题，两者间有何联系呢。

 

日本东京大学的科学家们意外的发现p53与microRNA的另一种调控关系，在DNA受到损失时，p53能增强几种抑制生长的microRNA的转录成熟，包括miR-16-1、miR-143和miR-145。这些microRNA的活性受p53的调控，而这些生物事件是癌症发生中的关键因素。

 

研究小组认为这一结果首次发现了p53对microRNA的调控机制，这些机制可能是解答某些癌症机制问题的关键。

（生物通 小茜）

 

全球首推Sanger microRNA阵列检测服务 一站式服务 点击索取资料

 

生物通推荐原文检索：

Modulation of microRNA processing by p53

 

Hiroshi I. Suzuki1, Kaoru Yamagata2,3, Koichi Sugimoto4, Takashi Iwamoto5, Shigeaki Kato2,3 & Kohei Miyazono1

Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan

Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

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

 

【Abstract】

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.