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

• Authors: Yujing Li, Emory University; Li Lin, Emory University; Zigang Li, The University of Chicago; Xuecheng Ye, University of Texas; Ke Xiong, University of Texas; Baikuntha Aryal, The University of Chicago; Zihui Xu, Emory University; Zain Paroo, University of Texas; Qinghua Liu, University of Texas; Chuan He, The University of Chicago; Peng Jin, Emory University
• Journal Title: Cell Metabolism
• Volume: Volume 15, Number 6
• Publisher: Elsevier (Cell Press): 12 month embargo | 2012-06-06, Pages 895-904
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.cmet.2012.04.021
• Subjects: Biology, Genetics; Chemistry, Biochemistry

Abstract

SUMMARY 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.