title: RNA regulons in Hox 5' UTRs confer ribosome specificity to gene regulation.
abstract: Emerging evidence suggests that the ribosome has a regulatory function in directing how the genome is translated in time and space. However, how this regulation is encoded in the messenger RNA sequence remains largely unknown. Here we uncover unique RNA regulons embedded in homeobox (Hox) 5' untranslated regions (UTRs) that confer ribosome-mediated control of gene expression. These structured RNA elements, resembling viral internal ribosome entry sites (IRESs), are found in subsets of Hox mRNAs. They facilitate ribosome recruitment and require the ribosomal protein RPL38 for their activity. Despite numerous layers of Hox gene regulation, these IRES elements are essential for converting Hox transcripts into proteins to pattern the mammalian body plan. This specialized mode of IRES-dependent translation is enabled by an additional regulatory element that we term the translation inhibitory element (TIE), which blocks cap-dependent translation of transcripts. Together, these data uncover a new paradigm for ribosome-mediated control of gene expression and organismal development.
authors.affiliation: 1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA [3] Tetrad Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Siqi
authors.initials: S
authors.lastname: Tian
authors.affiliation: 1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Wipapat
authors.initials: W
authors.lastname: Kladwang
authors.affiliation: 1] Department of Biochemistry, Stanford University, Stanford, California 94305, USA [2] Department of Physics, Stanford University, Stanford, California 94305, USA.
authors.forename: Rhiju
authors.initials: R
authors.lastname: Das
authors.affiliation: 1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Barna
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics; D012315:RNA Caps / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D015027:Zebrafish / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D012315:RNA Caps; C558903:RPL38 protein, mouse; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins