title: Differential Sensitivity of Target Genes to Translational Repression by miR-17~92.
abstract: MicroRNAs (miRNAs) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree, but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA. Here, we conducted an integrated analysis of transcriptome and translatome of primary B cells from mutant mice expressing miR-17~92 at three different levels to address this issue. We found that target genes exhibit differential sensitivity to miRNA suppression and that only a small fraction of target genes are actually suppressed by a given concentration of miRNA under physiological conditions. Transgenic expression and deletion of the same miRNA gene regulate largely distinct sets of target genes. miR-17~92 controls target gene expression mainly through translational repression and 5'UTR plays an important role in regulating target gene sensitivity to miRNA suppression. These findings provide molecular insights into a model in which miRNAs exert their specific functions through a small number of key target genes.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.|Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Hyun Yong
authors.initials: HY
authors.lastname: Jin
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Oda
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Pengda
authors.initials: P
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Chao
authors.identifier: 0000-0002-2384-2900
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Xiaojuan
authors.identifier: 0000-0002-6632-3297
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Division of Biomedical Convergence/Institute of Bioscience & Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Seung Goo
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Valentine
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.|Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Jennifer M
authors.identifier: 0000-0002-6818-4673
authors.initials: JM
authors.lastname: Kefauver
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Lujian
authors.initials: L
authors.lastname: Liao
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yaoyang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Alicia
authors.initials: A
authors.lastname: Gonzalez-Martin
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Jovan
authors.initials: J
authors.lastname: Shepherd
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Gareth J
authors.identifier: 0000-0002-1275-2010
authors.initials: GJ
authors.lastname: Morgan
authors.affiliation: Next Generation Sequencing Core, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Tony S
authors.identifier: 0000-0002-2809-3187
authors.initials: TS
authors.lastname: Mondala
authors.affiliation: Next Generation Sequencing Core, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Head
authors.affiliation: Department of Molecular Bioscience/Institute of Bioscience & Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Pyeung-Hyeun
authors.initials: PH
authors.lastname: Kim
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Nengming
authors.identifier: 0000-0001-5417-707X
authors.initials: N
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Wen-Hsien
authors.initials: WH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: James R
authors.identifier: 0000-0002-8772-468X
authors.initials: JR
authors.lastname: Williamson
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.|State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Changchun
authors.identifier: 0000-0001-8754-3208
authors.initials: C
authors.lastname: Xiao
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015151:Immunoblotting; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II