Mammalian Polycistronic mRNAs and Disease

详细信息    查看全文

• 作者：Timofey A. Karginov¹ ; ³ ; Daniel Parviz Hejazi Pastor¹ ; ³ ; Bert L. Semler² ; Christopher M. Gomez¹ ; ^{cgomez@neurology.bsd.uchicago.edu}
• 关键词：bicistronic ; polycistronic ; IRES ; ITAF ; eIF ; cap-independent
• 刊名：Trends in Genetics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：33
• 期：2
• 页码：129-142
• 全文大小：2299 K
• 卷排序：33

文摘

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.