Combinatorial aspects of RNA design

Mathematical Biology Seminar
Friday, January 22, 2021 - 3:00pm for 1 hour (actually 50 minutes)
Yann Ponty – Ecole Polytechnique France – Yann.Ponty@lix.polytechnique.fr
Afaf Saaidi

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RiboNucleic Acids (RNAs) are ubiquitous, versatile, and overall fascinating, biomolecules which play central roles in modern molecular biology. They also represent a largely untapped potential for biotechnology and health, substantiated by recent disruptive developments (mRNA vaccines, RNA silencing therapies, guide-RNAs of CRISPR-Cas9 systems...). To address those challenges, one must effectively  perform RNA design, generally defined as the determination of an RNA sequence achieving a predefined biological function.

I will focus in this talk on algorithmic results and enumerative properties stemming from the inverse folding, the problem of designing a sequence of nucleotides that fold preferentially and uniquely (with respect to base-pair maximization) into a target secondary structure. Despite the NP-hardness of the problem (+ absence of a Fixed Parameter-Tractable algorithm) we showed that it can be solved in polynomial time for restricted families of structures. Such families are dense in the space of designable 2D structures, so that any structure that admits a solution for the inverse folding can be efficiently designed in an approximated sense.

We show that any 2D structure avoiding two forbidden motifs can be modified into a designable structure  by adding at most one extra base-pair per helix. Moreover, both the modification and the design of a sequence for the modified structure can be computed in linear time. Finally, if time allows, I will discuss combinatorial consequences of the existence of undesignable motifs. In particular, it implies an exponentially decreasing density of designable structures amongst secondary structures. Those results extend to virtually any design objectives and energy models.

This is joint work with Cédric Chauve, Jozef Hales, Jan Manuch, Ladislav Stacho (SFU, Canada), Alice Héliou, Mireille Régnier, and Hua-Ting Yao (Ecole Polytechnique, France).