| Literature DB >> 25734836 |
James Hemphill1,2, Qingyang Liu2, Rajendra Uprety2, Subhas Samanta1, Michael Tsang3, Rudolph L Juliano4, Alexander Deiters1,2.
Abstract
The spliceosome machinery is composed of several proteins and multiple small RNA molecules that are involved in gene regulation through the removal of introns from pre-mRNAs in order to assemble exon-based mRNA containing protein-coding sequences. Splice-switching oligonucleotides (SSOs) are genetic control elements that can be used to specifically control the expression of genes through correction of aberrant splicing pathways. A current limitation with SSO methodologies is the inability to achieve conditional control of their function paired with high spatial and temporal resolution. We addressed this limitation through site-specific installation of light-removable nucleobase-caging groups as well as photocleavable backbone linkers into synthetic SSOs. This enables optochemical OFF → ON and ON → OFF switching of their activity and thus precise control of alternative splicing. The use of light as a regulatory element allows for tight spatial and temporal control of splice switching in mammalian cells and animals.Entities:
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Year: 2015 PMID： 25734836 PMCID： PMC5545098 DOI： 10.1021/jacs.5b00580
Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419