On the Design of RNA Sequences for Realizing Extended Shapes

It is known that for two given secondary structures (defined by position of base pairings) an RNA string can easily be found that can fold into both structures. But for more than two secondary structures this is not necessarily possible. Moreover, when four or more secondary structures are given the problem to determine the least number of positions, such that after the removal of all incident base pairs, a compatible RNA sequence can be found, is known to be NP-complete (\cite{real_shapes}). In this paper we introduce pseudo edges that are used to forbid that certain base pairs can bind and therefore can be used to define the properties of possible RNA secondary structures. We study the complexity of the problem to design an RNA sequence that can fold into different secondary structures each of them is described by a set of required and forbidden base pairs. We refine the NP-completeness results of \cite{real_shapes} and show an analoguous NP-completeness result for the realization problem concerning the removal of (pseudo) edges. We also present a polynomial time method for checking the realizability of extended shape graphs. Furthermore, we empirically analyze the influence of pseudo edges on the realizability for sets of random RNA sequences and for sets of aptamers.

[1]  Emmanuel Loukakis A Dynamic Programming Algorithm To Test A Signed Graph For Balance , 2003, Int. J. Comput. Math..

[2]  Lauren Ancel Meyers,et al.  Aptamer Database , 2004, Nucleic Acids Res..

[3]  Luc Jaeger,et al.  Construction and characterization of a gold nanoparticle wire assembled using Mg2+-dependent RNA-RNA interactions. , 2006, Nano letters.

[4]  P. Clote,et al.  On realizing shapes in the theory of RNA neutral networks. , 2005, Journal of theoretical biology.

[5]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[6]  S. Silverman,et al.  Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA. , 2003, RNA.

[7]  F. Harary On the notion of balance of a signed graph. , 1953 .

[8]  I. Hofacker RNA Secondary Structure Analysis Using the Vienna RNA Package , 2003, Current protocols in bioinformatics.

[9]  R. Breaker,et al.  Engineering precision RNA molecular switches. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Mihalis Yannakakis,et al.  Edge-Deletion Problems , 1981, SIAM J. Comput..

[11]  D. W. Staple,et al.  Open access, freely available online Primer Pseudoknots: RNA Structures with Diverse Functions , 2022 .

[12]  U. von Ahsen Translational fidelity: error-prone versus hyper-accurate ribosomes. , 1998, Chemistry & biology.

[13]  Scott K. Silverman Nucleic Acid Switches and Sensors , 2006 .

[14]  P. Schuster,et al.  Generic properties of combinatory maps: neutral networks of RNA secondary structures. , 1997, Bulletin of mathematical biology.

[15]  Beatrix Suess,et al.  Synthetic riboregulators - an alternative means to control gene expression , 2005 .

[16]  P. Stadler,et al.  Design of multistable RNA molecules. , 2001, RNA.

[17]  Cody W. Geary,et al.  Computational and Experimental RNA Nanoparticle Design , 2009 .