==== Front Biochem Biophys RepBiochem Biophys RepBiochemistry and Biophysics Reports2405-5808Elsevier S2405-5808(18)30145-610.1016/j.bbrep.2018.07.004CorrespondenceInteractions between the prion protein and nucleic acids Wills Peter R. p.wills@auckland.ac.nzDepartment of Physics, University of Auckland, PB 92019, Auckland 1142, New Zealand11 7 2018 9 2018 11 7 2018 15 68 68 15 6 2018 3 7 2018 © 2018 The Author2018This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ==== Body In their recent report [1] concerning interactions between the prion protein (PrP) and nucleic acids, Bera and Biring present a number of RNA secondary structures which are erroneously described as pseudoknots. In the caption of Figure 2 it is stated "Normally, the pseudoknot contains two stems and three loops". An RNA pseudoknot is formed when the bases within a loop undergo Watson-Crick pairing with another otherwise single-stranded region of the same molecule [2]. The structures "MNV" in Figure 1 and "Hm45" and "Cm48" in Figure 2 of the Bera and Biring report [1] do not satisfy that criterion; they are simply multiple stem-loop structures. This in no way invalidates the experimental findings, but it does complicate the interpretation of them. Many pseudoknots are capable of adopting a variety of alternative conformations, sometimes involving triple-base interactions that are determinative in relation to protein binding, so a proper understanding of protein binding can only be achieved once the three dimensional structure of the RNA in the RNA-protein complex has been identified. The "classic pseudoknot" first postulated by this author [3] has never been verified experimentally, in spite of its possibility having been demonstrated across the wide phylogenetic spectrum of PrP mRNA species [4]. However, the binding of the HIV tat protein, among others, to the tandem repeat region of the PrP mRNA [5], [6] has been interpreted as indicative of a structure which is very different from the hypothetical pseudoknot, resembling instead the stemloop required for the tat-dependent transactivation of HIV [7]. The finding of Bira and Biring [1] that PrP can bind to the tandem repeat region of its own mRNA is very interesting in relation to hypothetical role of this interaction in the replication of the ætiological agent of transmissible spongiform encephalopathy through ribosomal frameshifting [8], [9]. On the other hand extensive experimental investigations (unpublished results) have so far failed to verify the existence of any special structural motifs—particular stemloops [8], pseudoknots [3] or G-quadraplexes [10]—that could facilitate such a process, highlighting the difficulty in progressing from calculated to actual RNA structures. ==== Refs References 1 Bera A. Biring S. A quantitative characterization of interaction between prion protein with nucleic acids Biochem. Biophys. Rep. 14 2018 114 124 29872743 2 Westhof E. Jaeger L. RNA Pseudoknots Curr. Opin. Struct. Biol. 2 1992 327 333 3 Wills P.R. Potential Pseudoknots in the PrP-encoding mRNA J. Theor. Biol. 159 1992 523 527 1296103 4 Barrette I. Poisson G. Gendron P. Major F. Pseudoknots in prion protein mRNAs confirmed by comparative sequence analysis and pattern searching Nucleic Acids Res. 29 2001 753 758 11160898 5 Scheffer U. Okamoto T. Forrest J.M.S. Rytik P.G. Müller W.E.G. Schröder H.C. Interaction of 68 kDa TAR RNA-binding protein and other cellular proteins with prion protein-RNA stem-loop J. Neurovirol. 1 1995 391 398 9222382 6 Müller W.E.G. Scheffer U. Perovica S. Forrest J. Schröder H.C. Interaction of prion protein mRNA with CBP35 and other cellular proteins. Possible implications for prion replication and age-dependent changes Arch. Gerontol. Geriatr. 25 1997 41 58 15374100 7 Wills P.R. Hughes A.J. Stem loops in HIV and prion protein mRNAs J. Acquir. Immune Def. Syndr. 3 1990 95 97 8 Wills P.R. Induced frameshifting mechanism of replication for an information-carrying scrapie prion Microb. Pathog. 6 1989 235 249 2502700 9 Wills P.R. Frameshifted prion proteins as pathological agents: quantitative considerations J. Theor. Biol. 325 2013 52 61 23454079 10 Olsthoorn R.C.L. G-quadruplexes within prion mRNA: the missing link in prion disease? Nucl. Acids Res. 42 2014 9327 9333 25030900