eferences 153Up to now, the number of artificially engineered systems used to control pre-
mRNA splicing is limited, but the examples presented impressively demonstrate
that synthetic devices have an immense potential for controlling splicing and,
thus, both level and identity of target gene expression.
7.9 Conclusion
Besides the importance of splicing for increasing proteome diversity, there is a
clear impact of introns on gene expression levels with introns often stimulating
but sometimes also reducing gene expression. There is no universal requirement
for introns, but their presence has to be carefully considered during the de novo
design of genetic pathways. Moreover, given the great importance of RNA splic-
ing for gene regulation per se, RNA elements that target splicing may soon provide
general and highly applicable platforms for engineering gene regulation systems.
Acknowledgments
This work has been supported by grants of the Deutsche Forschungsgemeinschaft
(CRC902 A2 B.S. and B14 J.E.W.) and the Else Kröner-Fresenius-Stiftung (J.E.W.).
Definitions
Splicing removal of intronic sequences from the pre-mRNA
Exon sequences of a gene included into the mature mRNA
Intron intervening sequences removed upon splicing
Spliceosome machinery that removes introns from the pre-mRNA
Alternative splicing generation of multiple mature mRNA molecules from a
single gene
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