UNEARTHING THE BURIED TRESASURES-COMPUTATIONAL IDENTIFICATION AND ANALYSIS OF NONCODING RNAS

The central dogma of molecular biology states that the genetic information flows from DNA to RNA to protein. This dogma has exerted a substantial influence on our understanding of the genetic activities in the cells. Under this influence, the prevailing assumption until the recent past was that genes are basically repositories for protein coding information, and proteins are responsible for most of the important biological functions in all cells. In the meanwhile, the importance of RNAs has remained rather obscure, and the RNA was mainly viewed as a passive intermediary that bridges the gap between DNA and protein. Except for classic examples such as tRNAs (transfer RNAs) and rRNAs (ribosomal RNAs), functional noncoding RNAs were considered to be rare. However, this view has experienced a dramatic change during the last decade, as systematic screening of various genomes identified myriads of noncoding RNAs (ncRNAs), which are RNA molecules that function without being translated into proteins [11, 40]. It has been realized that many ncRNAs play important roles in various biological processes. As RNAs can interact with other RNAs and DNAs in a sequence-specific manner, they are especially useful in tasks that require highly specific nucleotide recognition [11]. Good examples are the miRNAs (microRNAs) that regulate gene expression by targeting mRNAs (messenger RNAs) [4, 20] , and the siRNAs (small interfering RNAs) that take part in the RNAi (RNA interference) pathways for gene silencing [29, 30]. Recent developments show that ncRNAs are extensively involved in many gene regulatory mechanisms [14, 17]. The roles of ncRNAs known to this day are truly diverse. These include transcription and translation control, chromosome replication, RNA processing and modification, and protein degradation and translocation [40], just to name a few. These days, it is even claimed that ncRNAs dominate the genomic output of the higher organisms such as mammals, and it is being suggested that the greater portion of their genome (which does not encode proteins) is dedicated to the control and regulation of cell development [27]. As more and more evidences pile up, greater attention is paid to ncRNAs, which have been neglected for a long time. Researchers began to realize that the vast majority of the genome that was regarded as “junk”, mainly because it was not well understood, may indeed hold ∗Both authors are with the Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. †Work supported in parts by the NSF grant CCF-0428326 and the Microsoft Research Graduate Fellowship.