Messenger RNA repair and restoration of protein function by spliceosome-mediated RNA trans-splicing.
The functional repertoire of the human genome is amplified by the differential assortment of exons. Spliceosome-mediated RNA trans-splicing can mobilize these packets of genetic information to reprogram mRNAs. In principle, this process could repair defective transcripts in loss-of-function genetic disorders in humans. We developed a tractable lacZ repair system to serve as a model for these genetic disorders. Targeted pre-trans-splicing RNA molecules efficiently and specifically repaired mutated lacZ transcripts and restored enzymatic activity in human cells. The development of this model confirms the potential for spliceosome-mediated RNA trans-splicing in genetic repairs and provides a powerful tool for rational design and in vitro evolution of pre-trans-splicing molecules.
Puttaraju, M; DiPasquale, J; Baker, CC; Mitchell, LG; Garcia-Blanco, MA
Volume / Issue
Start / End Page
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)