Alternative splicing at NAGNAG acceptors: simply noise or noise and more?

Alternative splicing at pairs of acceptors in close proximity are one frequent cause of transcriptome complexity. In particular, acceptors with the pattern NAGNAG are widespread in several genomes [1–3]. When affecting the coding regions, alternative splicing at NAGNAGs mainly results in the insertion/deletion of one amino acid. While such subtle events are undoubtedly frequent, an important question arises: do they have functional consequences or are they simply noise tolerated by cells? Zavolan and colleagues [3,4] suggest that these variations are the result of stochastic binding of the spliceosome at neighboring splice sites and do not discuss known functional implications. We previously found indications against a general noise assumption for NAGNAG splice events [1]: biases towards intron phase 1 and single amino acid

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