title: ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages.
abstract: Posttranscriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology, and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (HuR), we mapped miRNA binding sites at the transcriptome-wide scale in wild-type and Elavl1 knockout murine bone-marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/endothelial crosstalk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3' UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (Tristetraprolin). Thus, the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of posttranscriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis, and tissue homeostasis.
authors.affiliation: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Hafner
authors.affiliation: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.affiliation: Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. Electronic address: tih2002@med.cornell.edu.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hla
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D000067780:ELAV-Like Protein 1; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D059467:Transcriptome; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D051816:Tristetraprolin; C497553:Zfp36 protein, mouse