Iron homeostasis regulates the activity of the microRNA pathway through poly(C)-binding protein 2.
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.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Yujing
Y
Li
Li
L
Lin
Zigang
Z
Li
Xuecheng
X
Ye
Ke
K
Xiong
Baikuntha
B
Aryal
Zihui
Z
Xu
Zain
Z
Paroo
Qinghua
Q
Liu
Chuan
C
He
Peng
P
Jin
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D015365:Enoxacin / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D041681:NIH 3T3 Cells; D055503:Protein Multimerization; D034622:RNA Interference / Q000187:drug effects*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism
D007502:Iron Chelating Agents; D035683:MicroRNAs; C501903:PCBP2 protein, human; D016601:RNA-Binding Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D015365:Enoxacin; D015082:2,2'-Dipyridyl; D007501:Iron; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D003676:Deferoxamine