Making Proteins: Recursive Splicing of Long Introns

Genes are made up of sections of DNA sequences that have different functions. Two of the sections are alternating sequences of codons and introns; codons contain the information needed to make proteins while introns are intervening DNA sequences with functions that are still poorly understood.

To go from DNA to complete proteins, introns need to be removed from the genes and exons need to be joined together when DNA is translated into mRNA. (See this conceptual drawing.) Any mistakes in the excision of introns can render a protein less effective or cause disease. Researchers have discovered a recursive splicing method in fruit flies that snips out long introns from large genes.

The recursive splicing method relies on cell machinery to recognize ratchetting points of unique mRNA sequences within long introns that lie between exons in a gene. Going from one ratchetting point to the next, small bits of introns form lariats that are each removed until the protein-encoding exons are joined together.

Antonio-Javier Lopez, professor of biological sciences at Carnegie Mellon University, said,

“Current data indicate that at least 15 percent of disease-causing mutations occur at standard signals where intron removal takes place through direct splicing. Mutations at recursive splice sites may cause additional diseases, but until now we haven’t looked for them.”

The removal of introns and splicing together of exons to form coding sequences for proteins is just part of the story. Up to 99% of human gene sequences are introns and while they were previously regarded as “junk DNA,” scientists are now starting to recognize their importance. The Intron Sequence and Information database (ISIS) is the first multiple organism nuclear intron database. Eventually, introns will move out of the shadow of exons and assume a place in the limelight.

PhysOrg.com, August 22, 2005