title: Global analyses of the effect of different cellular contexts on microRNA targeting.
abstract: MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development-with its resulting diversity of cellular contexts-impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3' UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3' UTR isoforms revealed that they influence ∼10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3' UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3' UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.|Department of Life Science, College of Natural Science and Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Jin-Wu
authors.initials: JW
authors.lastname: Nam
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Olivia S
authors.initials: OS
authors.lastname: Rissland
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: David
authors.initials: D
authors.lastname: Koppstein
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), CINVESTAV, Irapuato, Guanajuato 36824, México.
authors.forename: Cei
authors.initials: C
authors.lastname: Abreu-Goodger
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Calvin H
authors.initials: CH
authors.lastname: Jan
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Agarwal
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Muhammed A
authors.initials: MA
authors.lastname: Yildirim
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Howard Hughes Medical Institute.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D011110:Polymorphism, Genetic; D020871:RNA Stability; D015398:Signal Transduction; D014529:Uridine / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D014529:Uridine