Multiple E2F-Induced MicroRNAs Prevent Replicative Stress in Response to Mitogenic Signaling

• DOI: 10.1128/mcb.01372-09
• Publication Date: 2010-04-20T02:26:05Z
• Authors: María J. Bueno; Marta Gómez de Ce...; Usua Laresgoiti; José Fernández-Pi...; Ana M. Zubiaga; Marcos Malumbres
• Keywords: E2F; E2F1

Transcription of microRNAs (miRNAs) is thought to be regulated similarly that protein-coding genes. However, how miRNAs are during the cell division cycle not well understood. We have analyzed transcription profiles in response mitogenic stimulation primary fibroblasts. About 33% expressed these cells induced upon exit from quiescence. Many specifically by E2F1 or E2F3 G(1)/S transition and repressed E2F1/3-knockout cells. At least four miRNA clusters, let-7a-d, let-7i, mir-15b-16-2, mir-106b-25, direct targets E2F1/3-null Interestingly, do contribute E2F-dependent entry into S phase but rather inhibit targeting multiple regulators E2F targets. In fact, expression results a significant increase S-phase DNA damage absence microRNAs. Thus, E2F-induced limiting cellular responses activation, thus preventing replicative stress. Given known function inducing other oncogenic miRNAs, control likely play roles proliferation proliferative diseases such as cancer.