What is RNA splicing

via a “messenger” RNA intermediate

“introns”. The coding sequences are then called “exons”

gene and must be removed by a process called “RNA splicing”

small RNAs)

Splicing works similarly in different organisms, for example in yeast, flies, worms, plants and animals.

has to be transported to the cytoplasm to produce proteins

Ribosomes are RNA-protein machines that make proteins, translating the coding information in the mRNA

be removed before the mRNA can be translated to produce protein

example in different tissues.

Thus one gene can encode more than one protein. The proteins are similar but not identical and may have distinct properties. This is important in complex organisms

pre-mRNA

form in particular positions to give alternative splicing

We are studying how mRNAs and proteins interact in order to understand how these machines work in general and, in particular, how RNA splicing is regulated as it affects which proteins are produced in each cell and tissue in the body.

death)

(+)

(-)

single primary transcript

Combinatorial selection of one exon at each of four variable regions generates more than
38,000 different mRNAs and proteins in the Drosophila cell adhesion molecule Dscam

The protein variants are important for wiring of the nervous system and for immune response

protein

mRNA

pre-mRNA

the DNA
(in a gene)

mutation A
truncated mRNA

mutation B
exon 3 skipped

mutation C
longer exon 4

no mutation
normal mRNA

normal protein
active

truncated protein
inactive

protein of different size (smaller or longer)
inactive or aberrant function

categories

 Mutations affecting proteins that are involved in splicing
Examples: Spinal Muscular Atrophy
Retinitis Pigmentosa
Myotonic Dystrophy
 Mutations affecting a specific messenger RNA and disturbing its normal splicing pattern
Examples: ß-Thalassemia
Duchenne Muscular Dystrophy
Cystic Fibrosis
Frasier Syndrome
Frontotemporal Dementia and Parkinsonism