Iron Homeostasis Regulates the Activity of the MicroRNA Pathway through Poly(C)-Binding Protein 2

• Published in: Cell metabolism Vol. 15; no. 6; pp. 895 - 904
• Main Authors: Li, Yujing, Lin, Li, Li, Zigang, Ye, Xuecheng, Xiong, Ke, Aryal, Baikuntha, Xu, Zihui, Paroo, Zain, Liu, Qinghua, He, Chuan, Jin, Peng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.06.2012
• Subjects: 2,2'-Dipyridyl - pharmacology; Animals; biogenesis; chelating agents; DEAD-box RNA Helicases - metabolism; Deferoxamine - pharmacology; Enoxacin - pharmacology; gene expression; Gene Knockdown Techniques; Genes, Reporter; Green Fluorescent Proteins - biosynthesis; Green Fluorescent Proteins - genetics; HEK293 Cells; Homeostasis; Humans; iron; Iron - metabolism; Iron Chelating Agents - pharmacology; messenger RNA; Mice; microRNA; MicroRNAs - metabolism; NIH 3T3 Cells; Protein Multimerization; Ribonuclease III - metabolism; RNA Interference - drug effects; RNA Processing, Post-Transcriptional; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; translation (genetics)
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2012.04.021

MicroRNAs (miRNAs) control gene expression by promoting degradation or repressing translation of target mRNAs. The components of the miRNA pathway are subject to diverse modifications that can modulate the abundance and function of miRNAs. Iron is essential for fundamental metabolic processes, and its homeostasis is tightly regulated. Here we identified iron chelators as a class of activator of the miRNA pathway that could promote the processing of miRNA precursors. We show that cytosolic iron could regulate the activity of the miRNA pathway through poly(C)-binding protein 2 (PCBP2). PCBP2 is associated with Dicer and promotes the processing of miRNA precursors. Cytosolic iron could modulate the association between PCBP2 and Dicer, as well as the multimerization of PCBP2 and its ability to bind to miRNA precursors, which can alter the processing of miRNA precursors. Our findings reveal a role of iron homeostasis in the regulation of miRNA biogenesis. [Display omitted] ► Metal chelators enhance the activity of the shRNA-mediated RNAi pathway ► Cytosolic iron modulates the processing of shRNAs and miRNA precursors ► PCBP2 promotes miRNA biogenesis ► Cytosolic iron modulates PCBP2 association with Dicer and pre-miRNAs