RNA Partial Degradation Problem: Motivation, Complexity, Algorithm

Abstract

Studies conducted during the last decade unexpectedly revealed several new biological functions of RNA molecules. The involvement of RNA in many complex processes requires highly effective systems controlling its accumulation. In this context, the mechanisms of degradation appear as one of the most important factors influencing RNA activity. Here, we present our first attempt to describe the RNA degradation process using bioinformatics methods. Based on the obtained data, we propose a formulation of a new problem, called RNA Partial Degradation Problem (RNA PDP) and the algorithm that is capable of reconstructing an RNA molecule using the results of biochemical analysis of its degradation. In addition, we present the results of biochemical experiments and computational tests.

Tabu Search for the RNA Partial Degradation Problem

“…The objective of the RNA PDP is to reconstruct the original molecule by determining from this limited information the exact positions of the primary and secondary cleavage sites. More details can be found in the work of Blazewicz et al (2011).…”

“…The decision version of the RNA PDP is to determine whether there is a C-consistent pair (P 1 , P 2 ) with D and Z. It was proved by Blazewicz et al (2011) that the problem is strongly NP-complete when no errors are allowed (i.e., when C = 0). The computational complexity of the modified problem with R = R(P 1 ) is not formally determined yet, but presumably it remains strongly NP-complete even without any errors allowed.…”

“…Many problems that have arisen in this discipline have been classified as computationally hard (i.e., unlikely to be solved optimally in polynomial time). We consider one of them, namely, the RNA partial degradation problem (RNA PDP for short), proved to be strongly NP-hard, in which the primary actor is the ribonucleic acid (RNA) subjected to a nonenzymatic hydrolysis experiment (Blazewicz et al, 2011).…”

“…Our focus is on biochemical experiments that use in vitro systems, since it is not possible to study all aspects of this process in a living organism using methods currently available. Blazewicz et al (2011) analyzed the degradation patterns of two artificial RNA molecules applying commonly used experimental methods (Dutkiewicz and Ciesiolka, 2005;Rybarczyk et al, 2016;Adachi and Yu, 2014). As a result of the partial degradation process, many copies of an RNA molecule are cleaved into a collection of fragments of the original molecule.…”

Bioinformatics and Computational Biology in Poland

“…Paweł Wojciechowski is developing GPU-based algorithms for various aspects of sequence alignment and next-generation sequence data analysis [70]. The Błażewicz group is also working on other aspects of computational biology, such as modeling of RNA metabolism [71] and modeling of viral infections [72]. Ryszard W. Adamiak's group at IBCh PAS is working on biomolecular NMR (Zofia Gdaniec) and molecular dynamics simulations (Tadeusz Kuliński) of RNA, and in collaboration with the Błażewicz team (with Marta Szachniuk), they are involved in the development and application of tools for RNA 3D structure modeling [73], [74], and in NMR spectra analysis.…”