Computational Studies of Non-coding Rnas

Until recently, RNA has been viewed as a simple “working copy” of the genomic DNA, simply transporting information from the genome into the proteins. In the 1980s, this picture changed, to certain extent, with the discovery of ribozymes and the realization that the ribosome is essentially an “RNA machine”. Since the turn of the millenium, however, RNA has moved from a fringe topic to a central research topic following the discovery of RNA interference (RNAi), the post transcriptional silencing of gene expression via interactions between mRNAs and their regulatory RNAs. More recent studies have revealed that a large fraction of the genome sequences give rise to RNA transcripts that do not code for proteins. Those RNAs that do not code for proteins are called non-coding RNAs (ncRNAs). A recent computational screen estimated the number of small regulatory RNAs, which form an important class of non-coding RNAs, in Arabidopsis thaliana to be in the order of 75,000. Among small RNAs, two subclasses form the bulk of all regulatory RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs) — which are of similar length (21 to 25 nt) and composition but different by origin. It is predicted that these two subclasses regulate at least one-third of all human genes. There are many other classes of non-coding RNAs with functionalities beyond simple regulation of gene expression: examples include snoRNAs, snRNAs, gRNAs, and stRNAs, which respectively perform ribosomal RNA (rRNA) modification, RNA editing, mRNA splicing and developmental regulation. Even for these well-studied RNAs, their precise mode of function remains poorly understood. In addition to such endogenous ncRNAs, antisense oligonucleotides have been used as exogenous inhibitors of gene expression; antisense technology is now commonly used for therapeutic purposes and as a research tool. The therapeutic objective of antisense technology is to block the production of disease-causing proteins. In principle, these artificial regulatory RNA molecules could be employed as drugs for the treatment of a variety of human diseases including various types of cancer, rheumatoid arthritis, brain diseases, and viral infections. As a research tool, antisense nucleic acids may be used to study metabolic networks by controling or interfering with the dynamics and function of various modules in the network. Furthermore,