The Splicing Codes

One of the greatest surprises of molecular biology was the discovery that the primary transcripts of the genes are often transformed into messenger RNAs by removing some RNA strings (called introns) and by joining together the remaining pieces (the exons). The result is a true assembly, because exons are assembled into messengers, and we need, therefore, to find out if it is a catalyzed assembly (like transcription) or a codified assembly (like translation). In the first case the cutting and sealing operations, collectively known as splicing, would require only a catalyst (comparable to RNA polymerase), whereas in the second case they would need a catalyst and a set of adaptors (comparable to ribosome and tRNAs).

This suggests immediately that splicing is a codified process because it is implemented by structures that are very similar to those of protein synthesis. The splicing systems, known as spliceosomes, are huge molecular machines like ribosomes, and employ small molecular structures, known as snRNAs or snurps, which are very much comparable to tRNAs. The similarity, however, goes much deeper than that, because the snRNAs have properties that fully qualify them as adaptors. They bring together, in a single molecule, two independent recognition processes, one for the beginning and one for the end of each intron, thus creating a specific correspondence between the world of the primary transcripts and the world of messengers.

The two recognition steps are independent not only because there is a physical distance between them, but above all because the first step could be associated with different types of the second one, as demonstrated by the cases of alternative splicing. The choice of the beginning and of the end of an intron, furthermore, is the operation that actually defines the introns and gives them a meaning. Without a complete set of such operations, primary transcripts could be transformed arbitrarily into messenger RNAs, and there would be no biological specificity whatsoever.

In RNA splicing, in conclusion, we find the three basic characteristics of all codes: (1) a correspondence between two independent worlds; (2) the presence of molecular adaptors; and (3) a set of rules that guarantee biological specificity. We conclude therefore that the processing of RNA transcripts into messengers is truly a codified process based on adaptors, and takes place with rules that can rightly be given the name of splicing codes (Barbieri, 1998; 2003).

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