RNAanalyzer3 Maps RNA Structure and Motifs Across All Living Organisms

A team of researchers from the University of Würzburg has developed a new computational tool that enables a more complete analysis of ribonucleic acid (RNA), where structure plays a decisive role in function. The work, led by Thomas Dandekar and Kathi Zarnack, is published in Nucleic Acids Research.

RNA controls many vital cellular processes, and when its structure goes awry, disease can follow. Many existing computer programs analyze only individual sections of an RNA molecule. The new tool, called RNAanalyzer³, takes a holistic approach: it evaluates both the sequence of nucleotide building blocks and the entire molecular structure—and places the resulting motifs in a biological context.

RNAanalyzer³ works for all living organisms as well as for viruses, allowing researchers to compare, for example, a virus that affects humans against one that infects plants in a single workflow. "This saves an enormous amount of time," said lead author Aman Akash.

Another step forward is how results are displayed. Instead of presenting a string of A, C, G, and U nucleotides, the program produces interactive, color-coded maps of the RNA.

"This allows researchers to see immediately where the strand forms loops or where important control centers are located," said Professor Dandekar. Motifs—short patterns within an RNA strand that act as docking sites for cellular machinery—are particularly important in this kind of analysis. The team illustrated the tool's performance with two case studies.

In the FTH1 gene, which controls iron storage, RNAanalyzer³ correctly identified the IRE motif, a control center with medical relevance because cancer cells can exploit iron metabolism to grow more quickly. In the TNF gene, which regulates inflammatory responses, the tool flagged ARE motifs at the rear of the RNA, a region known to determine RNA stability. 

RNAanalyzer³ is written in the Perl programming language and pulls patterns from large international databases such as Rfam and miRbase, comparing known motifs against new samples.

"Compared to other programs, RNAanalyzer³ makes fewer incorrect predictions because it combines structure and context," said Professor Zarnack.

There are some technical limits to the tool. Exact fold calculations are restricted to sequences of up to 5,000 nucleotides; broader pattern searches run to 20,000; and users can analyze up to five sequences simultaneously.