Splicing Regulation
RNA splicing is a post-transcriptional process where protein coding exons in the initial pre-mRNA are joined together, while the intervening intronic sequences are spliced out. The splicing process is highly complex and is regulated by a large number of proteins.
The splice sites are defined by relatively conserved sequences, which allows recognition by the spliceosome. However, splicing enhancer and silencer elements are necessary for the regulation of splicing. These are cis-acting elements binding splicing regulatory proteins, and these sites define the so-called splicing code, which determines the splicing outcome.
The alternative splicing which is the result of this dynamic regulation increases the number of proteins which can be encoded by the human genome and therefore is important for human complexity.
To be able to decipher the splicing code we did RNA binding studies and created a map of hnRNP A1 binding sites:
Bruun et al., BMC Biology, Jul 2016
And based on in vivo binding studies, we developed a computational tool to predict binding of a large number of RNA binding proteins to RNA using only sequence input:
Grønning et al., Nucleic Acids Research, Jun 2020
Exon Vulnerability
Mutations in exonic splicing regulatory elements may affect the delicate regulation of RNA splicing, and it is widely accepted that such mutations can cause aberrant splicing and in some cases lead to disease. However, we have shown that not all exons are equally vulnerable to these mutations
Holm et al., Human Mutation, Feb 2022
We developed the computational tool VulExMap to identify constitutive exons which are vulnerable to exonic splice mutations:
Holm et al., Nucleic Acids Research, May 2024
