|ZFIN ID: ZDB-PUB-170214-210|
Conditional control of alternative splicing through light-triggered splice-switching oligonucleotides
Hemphill, J., Liu, Q., Uprety, R., Samanta, S., Tsang, M., Juliano, R.L., Deiters, A.
|Source:||Journal of the American Chemical Society 137: 3656-62 (Journal)|
|Registered Authors:||Tsang, Michael|
|PubMed:||25734836 Full text @ J. Am. Chem. Soc.|
Hemphill, J., Liu, Q., Uprety, R., Samanta, S., Tsang, M., Juliano, R.L., Deiters, A. (2015) Conditional control of alternative splicing through light-triggered splice-switching oligonucleotides. Journal of the American Chemical Society. 137:3656-62.
ABSTRACTThe 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.