Pseudogenes as an alternative source of natural antisense transcripts.
BACKGROUND
Naturally occurring antisense transcripts (NATs) are non-coding RNAs that may regulate the activity of sense transcripts to which they bind because of complementarity. NATs that are not located in the gene they regulate (trans-NATs) have better chances to evolve than cis-NATs, which is evident when the sense strand of the cis-NAT is part of a protein coding gene. However, the generation of a trans-NAT requires the formation of a relatively large region of complementarity to the gene it regulates.


RESULTS
Pseudogene formation may be one evolutionary mechanism that generates trans-NATs to the parental gene. For example, this could occur if the parental gene is regulated by a cis-NAT that is copied as a trans-NAT in the pseudogene. To support this we identified human pseudogenes with a trans-NAT to the parental gene in their antisense strand by analysis of the database of expressed sequence tags (ESTs). We found that the mutations that appeared in these trans-NATs after the pseudogene formation do not show the flat distribution that would be expected in a non functional transcript. Instead, we found higher similarity to the parental gene in a region nearby the 3' end of the trans-NATs.


CONCLUSIONS
Our results do not imply a functional relation of the trans-NAT arising from pseudogenes over their respective parental genes but add evidence for it and stress the importance of duplication mechanisms of genetic material in the generation of non-coding RNAs. We also provide a plausible explanation for the large transcripts that can be found in the antisense strand of some pseudogenes.
Max-Delbrück Center for Molecular Medicine, Robert Rössle Str, 10, 13125 Berlin, Germany. enrique.muro@mdc-berlin.de
Enrique M
EM
Muro
Miguel A
MA
Andrade-Navarro
D000818:Animals; D030541:Databases, Genetic; D019143:Evolution, Molecular; D020224:Expressed Sequence Tags; D006801:Humans; D011544:Pseudogenes / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics*
D016372:RNA, Antisense