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Pseudoknots in prion protein mRNAs confirmed by comparative sequence analysis and pattern searching
I Barrette1, G Poisson, P Gendron
1Département d'Informatique et de Recherche Opérationnelle, Université de Montréal, CP 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
Nucleic Acids Research
|February 13, 2001
Summary
The human prion gene
Area of Science:
- Molecular Biology
- Genetics
- Bioinformatics
Background:
- The human prion gene features a conserved 24-nucleotide repeat.
- RNA structure analysis suggests specific patterns within the prion gene's mRNA.
- Previous research predicted pseudoknots in human prion mRNA.
Purpose of the Study:
- To investigate RNA patterns, specifically pseudoknots, in prion gene mRNAs across species.
- To explore the potential role of these RNA structures in prion protein translation and disease.
Main Methods:
- Analysis of folding free energies of human prion mRNA.
- Identification and alignment of prion mRNA sequences from GenBank.
- Computer-generated three-dimensional structure modeling of prion pseudoknots.
Main Results:
- Pseudoknots were identified in prion mRNAs of various species, excluding birds and turtles.
- Co-variation analysis revealed conserved pseudoknot patterns despite low sequence homology.
- 3D modeling highlighted protein-RNA interaction domains within the human prion pseudoknot.
Conclusions:
- Pseudoknots are a conserved feature in many prion mRNAs, potentially acquired early in evolution.
- These structures may influence prion protein translation.
- The repeat region's pseudoknots are implicated in familial Creutzfeldt-Jakob disease.