Bioinformatics Bioinformatics Analysis Mutation

Changes in RNA Secondary Structure

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The importance of RNA structures has been observed in the life cycle of RNA-containing viruses, including the influenza virus. At least two regions of conserved secondary structure in NS segment (+) RNA are predicted to vary among influenza virus strains with respect to thermodynamic stability; both fall in the NS1 open reading frame. The NS1 protein is involved in multiple virus-host interaction processes, and its main function is to stop the cellular immune response to viral infection. 

One way to change the RNA secondary structure is to change the primary sequence. In the CDS, however, primary sequence changes necessarily alter codon usage, confounding any effects that might be attributable to changes in mRNA structure alone. An alternate means to affect secondary structure without changing codons is to incorporate modified nucleotides (nt) that maintain the same Watson–Crick base-pairing relationships but have small effects on local secondary structure. Such modified nucleotides can either stabilize or destabilize base pairs and hence overall mRNA structure.

The dynamic structure of RNA plays a central role in post-transcriptional regulation of gene expression such as; 

  • RNA maturation
  • Degradation
  • Translation
  • Splicing
  • microRNA biogenesis
  • RNA editing, and other biological processes

With the rise of next-generation sequencing, the study of RNA structure has been transformed from in vitro low-throughput RNA structure probing methods to in vivo high-throughput RNA structure profiling. The development of these methods enables incremental studies on the function of RNA structure to be performed, showing new insights of novel regulatory mechanisms of RNA structure in plants. 

Genome-wide scale RNA structure profiling allows us to investigate general RNA structural features over 10s of 1000s of mRNAs and to compare RNA structuromes between plant species. 

Steps

  • RNA structure probing methods
  • the biological functions of RNA structure
  • genome-wide RNA structural features corresponding to their regulatory mechanisms

RNA molecules fold into complex structures as a result of intramolecular interactions between their nucleotides. The function of many non-coding RNAs and some cis-regulatory elements of messenger RNAs highly depends on their fold. Single-nucleotide variants (SNVs) and other types of mutations can disrupt the native function of an RNA element by altering its base pairing pattern. Identifying the effect of a mutation on a RNA’s structure is, therefore, a crucial step in evaluating the impact of mutations on the post-transcriptional regulation and function of RNAs within the cell. Even though a single nucleotide variation can have striking impacts on the structure formation, interpreting and comparing the impact usually needs expertise and meticulous efforts. MutaRNA is a web server for visualization and interpretation of mutation-induced changes on the RNA structure in an intuitive and integrative fashion. 

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