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Nucleic Acids Research, 2001, Vol. 29, No. 3 753-758
© 2001 Oxford University Press

Pseudoknots in prion protein mRNAs confirmed by comparative sequence analysis and pattern searching

Isabelle Barrette, Guylaine Poisson, Patrick Gendron and François Major*

Département d’Informatique et de Recherche Opérationnelle, Université de Montréal, CP 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada

The human prion gene contains five copies of a 24 nt repeat that is highly conserved among species. An analysis of folding free energies of the human prion mRNA, in particular in the repeat region, suggested biased codon selection and the presence of RNA patterns. In particular, pseudoknots, similar to the one predicted by Wills in the human prion mRNA, were identified in the repeat region of all available prion mRNAs available in GenBank, but not those of birds and the red slider turtle. An alignment of these mRNAs, which share low sequence homology, shows several co-variations that maintain the pseudoknot pattern. The presence of pseudoknots in yeast Sup35p and Rnq1 suggests acquisition in the prokaryotic era. Computer generated three-dimensional structures of the human prion pseudoknot highlight protein and RNA interaction domains, which suggest a possible effect in prion protein translation. The role of pseudoknots in prion diseases is discussed as individuals with extra copies of the 24 nt repeat develop the familial form of Creutzfeldt–Jakob disease.

* To whom correspondence should be addressed at present address: Isis Pharmaceuticals Inc., 2292 Faraday Avenue, Carlsbad, CA 92008, USA. Tel: +1 760 603 2677; Fax: +1 760 431 2768; Email: major{at}iro.umontreal.ca The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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