In the last few years, there has been intense interest in RNA due to the surprising, previously unsuspected roles played by ribonucleic acid in what until now has been a predominantly protein-centric view of molecular biology. Apart from its roles as messenger RNA and transfer RNA, ribonucleic acid molecules play a catalytic role in the peptidyltransferase reaction in peptide bond formation and in intron splicing, both examples of enzymatic RNAs now termed ribonucleic enzymes or ribozymes. RNA plays a role in post-transcriptional gene regulation due to the hybridization of mRNA by small interfering RNAs (siRNA) and microRNAs (miRNA). By completely different means, RNA performs transcriptional and translational gene regulation by allostery, where a portion of the 5' untranslated region (5' UTR) of mRNA known as a riboswitch can undergo a conformational change upon binding a specific ligand such as adenine, guanine, or lysine. RNA is known to play critical roles in various other cellular mechanisms such as dosage compensation (XIST), protein shuttling (Blobel), expansion of the genetic code such as selenocysteine insertion, and ribosomal frameshift .
Illustrative of the growing recognition for the importance of RNA, the 2006 Nobel Prize in Physiology or Medicine was awarded to A.Z. Fire and C.C. Mello for their discovery of RNA interference and gene silencing by double-stranded RNA.
In this course, we present an overview of current computatioanl biology work on RNA. Beginning with the chemistry and biology of RNA, we will discuss combinatorial problems related with RNA secondary structure, free energy minimization algorithms, machine learning, statistical mechanics (Boltzmann partition function and sampling), noncoding RNA gene finders, and tertiary structure. The focus is to develop the mathematical and computational techniques to investigate biologically important aspects of RNA.
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