title: Inhibition of microRNA-302 (miR-302) by bone morphogenetic protein 4 (BMP4) facilitates the BMP signaling pathway.
abstract: The signaling pathway mediated by BMPs plays an essential role during development as well as the maintenance of homeostasis in adult. Aberrant activation or inactivation of BMP signaling can lead to developmental defects and various human disorders. To fine-tune its activity, BMP signaling is regulated both positively and negatively by extrinsic and intrinsic regulatory factors that modulate binding of ligand to the receptors, and the activity of receptors and their dedicated signal transducers, the Smad proteins. Upon BMP binding to the receptor complex, Smad proteins translocate to the nucleus and modulate gene expression transcriptionally by directly associating with the promoter region of target genes, or post-transcriptionally through modulation of microRNA (miRNA) synthesis. In this study, we demonstrate that BMP signaling down-regulates transcription of the miRNA-302∼367 gene cluster. We show that the type II BMP receptor (BMPRII) is a novel target of miR-302. Upon overexpression, miR-302 targets a partially complementary sequence localized in the 3'-untranslated region (UTR) of BMPRII transcripts and leads to destabilization of the transcripts and down-regulation of BMP signaling. We propose that the negative regulatory loop of BMP4-miR-302-BMPRII is a potential mechanism for the maintenance and fine-tuning of the BMP signaling pathway in various systems.
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Hara
authors.initials: H
authors.lastname: Kang
authors.forename: Justin
authors.initials: J
authors.lastname: Louie
authors.forename: Alexandra
authors.initials: A
authors.lastname: Weisman
authors.forename: Jessica
authors.initials: J
authors.lastname: Sheu-Gruttadauria
authors.forename: Brandi N
authors.initials: BN
authors.lastname: Davis-Dusenbery
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lagna
authors.forename: Akiko
authors.initials: A
authors.lastname: Hata
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001011:Aorta / Q000166:cytology; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D034622:RNA Interference; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D055415:Bone Morphogenetic Protein 4; C532169:MIRN302A microRNA, human; D035683:MicroRNAs