Pre-mRNA secondary structure and the regulation of splicing

Nuclear pre-mRNAs must be precisely processed to give rise to mature cytoplasmic mRNAs. This maturation process, known as splicing, involves excision of intron sequences and ligation of the exon sequences. One of the major problems in understanding this process is how splice sites, the sequences which form the boundaries between introns and exons, can be accurately selected. A number of studies have defined conserved sequences within introns which were later shown to interact with small nuclear ribonucleoproteins (snRNPs). However, due to the simplicity of these conserved sequences it has become clear that other elements must be involved and a number of studies have indicated the importance of secondary structures within pre-mRNAs. Using various examples, we shall show that such structures can help to specify splice sites by modifying physical distances within introns or by being involved in the definition of exons and lastly, that they can be part of the regulation of alternative splicing.