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Exon/intron should never be mixed up with coding/non-coding

Posted by pbio on 07 May 2009 at 22:28 GMT

Author: Jacques van Helden
Position: Prof.
Institution: Université Libre de Bruxelles
Submitted Date: November 27, 2008
Published Date: December 17, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

Response to "Where Do Introns Come From?"

Starting from the first sentence, this article relies on an erroneous definition of introns and exons, which contribute to propagate a too frequent mistake.

The following sentences are incorrect.

First sentence of the paper: "In eukaryotes (and viruses), genes may be organized into coding and noncoding regions, called exons and (spliceosomal) introns, respectively."

Box 1: "Spliceosomal introns are noncoding intervening sequences of eukaryotic and viral genes that are removed during the process of pre-mRNA maturation, leaving only coding sequence (exons) to be part of the messenger RNA."

Actually, there is no one-to-one correspondence between exon/intron and coding/non-coding regions of a gene. The concept of introns/exons is only defined by reference to the process of splicing, and not by reference to translation.

During RNA maturation, introns are indeed spliced out from the primary RNA, so it is correct to say that introns correspond to non-coding regions. Note that, in the case of alternative splicing, some introns contain coding regions, if "coding" is defined in term of information (a fragment of nucleic acids that contains the information to produce a polypeptide chain). However, the authors may argue that in the case where they are spliced out, these "potentially" coding introns will not contribute to produce a protein, and are thus not "actually" coding. If (and only if) we define "coding" as "actually producing a fragment of polypeptide", then we can agree when the authors say that introns are non-coding.

But the real problem lies in the second part of the definition: it is completely incorrect to say that exons correspond to coding regions. The messenger RNA that results from splicing contains both coding and non-coding fragments. Any mRNA contains untranslated regions on both extremities (5' and 3' UTRs). These UTRs can cover several tens to several hundreds of nucleotides. The first and the last exons thus always contain some piece of non-coding DNA. Moreover, non-coding exons are not even restricted to these first and last exons. Some UTRs can extend over several exons. These untranslated extremities should not be considered just as uninformative pieces of RNA hanging around the coding sequences: far from this, UTRs can play essential roles in mRNA maturation, stability, degradation, and in the regulation of translation.

I am pretty confident that the authors (as well as most readers) are perfectly aware of the distinction between exon/intron and coding/non-coding. The origin of the erroneous definition probably comes from a desire of simplification. Simplification should however never be at the cost of correctness. Defining concepts in a proper way is a difficult art, but a necessity, especially for an article targeting a large audience.

No competing interests declared.