title: Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication.
abstract: Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 > Cx26/30 > Cx26 > Cx31 > Cx30 = Cx-null. However, consistent with a uniform structure of miRNAs, there was no significant difference in permeability to different miRNAs. The passage is efficient; the miRNA level in the recipient cells could be up to 30% of the donor level. Moreover, the transferred miRNA is functional and could regulate gene expression in neighboring cells. Connexin mutation and gap junctional blockers could eliminate this miRNA intercellular transfer and gene regulation. These data reveal a novel mechanism for intercellular genetic communication. Given that connexin expression is cell-specific, this connexin-dependent, miRNA intercellular genetic communication may play an important role in synchronizing and coordinating proliferation and differentiation of specific cell types during multicellular organ development.
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536 U.S.A.
authors.forename: Liang
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536 U.S.A.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536 U.S.A.
authors.forename: Ruqiang
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536 U.S.A.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D042541:Intracellular Space; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D034443:RNA Transport / Q000187:drug effects
chemical_list: D017630:Connexins; D035683:MicroRNAs
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