title: Mammalian Polycistronic mRNAs and Disease.
abstract: Our understanding of gene expression has come far since the 'one-gene one-polypeptide' hypothesis proposed by Beadle and Tatum. In this review, we address the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment. We carried out a systematic literature review identifying 13 mammalian genes for which there is evidence for polycistronic expression via translation through an internal ribosome entry site (IRES). Although the canonical mechanism of translation initiation has been studied extensively, here we highlight a process of noncanonical translation, IRES-mediated translation, that is a growing source for understanding complex inheritance, the elucidation of disease mechanisms, and the discovery of novel therapeutic targets. Identification of additional polycistronic genes may provide new insights into disease therapy and allow for new discoveries of both translational and disease mechanisms.
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL, USA.
authors.forename: Timofey A
authors.initials: TA
authors.lastname: Karginov
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL, USA.
authors.forename: Daniel Parviz Hejazi
authors.initials: DPH
authors.lastname: Pastor
authors.affiliation: Department of Microbiology & Molecular Genetics, School of Medicine, University of California, Irvine, CA, USA.
authors.forename: Bert L
authors.initials: BL
authors.lastname: Semler
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL, USA. Electronic address: cgomez@neurology.bsd.uchicago.edu.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Gomez
mesh_terms: D000818:Animals; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000628:therapy; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000235:genetics*; D008322:Mammals; D058990:Molecular Targeted Therapy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000067556:Internal Ribosome Entry Sites; D012333:RNA, Messenger
keywords: IRES; ITAF; bicistronic; cap-independent; eIF; polycistronic