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.
Date: 2015
Source: Journal of the American Chemical Society   137: 3656-62 (Journal)
Registered Authors: Tsang, Michael
Keywords: none
MeSH Terms:
  • Alternative Splicing/radiation effects*
  • Animals
  • HeLa Cells
  • Humans
  • Light*
  • Oligonucleotides/chemistry
  • Oligonucleotides/genetics*
  • Zebrafish
PubMed: 25734836 Full text @ J. Am. Chem. Soc.
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.
ADDITIONAL INFORMATION