Predicting RNA Regulation: Challenges and Methods in Understanding Virulence in N. Meningitidis
The regulation of virulence genes in Neisseria meningitidis is closely linked to the role of small noncoding RNAs (sRNA). Traditional methods for predicting coding, tRNA, and rRNA genes are advanced, while sRNA prediction remains challenging due to factors like smaller size, sequence specificity, and misleading information. Our methodology combines comparative approaches with tailored scoring for RNA, utilizing tools like RFAM and Covariance Models to enhance RNA structure understanding. This comprehensive view aids in the prediction of RNA elements and their implications in bacterial virulence.
Predicting RNA Regulation: Challenges and Methods in Understanding Virulence in N. Meningitidis
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Presentation Transcript
DNA cis- or trans-regulatory trans-regulatory Antisense RNA Riboswitches CRISPR etc. RNA rRNA mRNA tRNA PROTEIN Why predict RNA? Regulation Protein Biosynthesis Noncoding RNA Traditional paradigm
Regulatory sRNA Hypothesis: Virulence in N. Meningitiditis is associated with regulation of virulence genes
sRNA Challenges Methods to predict coding, tRNA and rRNA genes are much more mature than those for sRNA. • less information • small • sequence-acting • misleading information • dual purpose • boundaries not obvious
Fundamental Methodology • Comparative • Analogous to protein comparative models • Scoring is tailored for RNA • Sequence-based weight matrices (RFAM) • Profile HMM • Structure-enhanced (Covariance Model) • Noncomparative • Search for transcriptional signals
Profile HMM • <Krogh figure>
RFAM • RNA database • Each RNA sequence classified in a Family • Families determined by Covariance Model (CM) • CM extends Profile HMM to include Covariance • Annotation of Families with Wikipedia
What is Covariance? • <MSA figure explaining covariance> • <secondary sequence explaining covariance-structure relationship>
Covariance Model • Extends Profile HMM to include basepairing information • <Figure>
Noncomparative Prediction • Transcription signals • <List types> • <Extend figure to include signals> • <Include binding example> • Limited utility because of …
Software Combined: may have relevance for predicting virulence
