Focus on RNA analysis

Until the 1990s, RNA was regarded only as a messenger between DNA and protein. The double helix of DNA was mostly getting the publicity on covers of magazines and other media, becoming a symbol of life. It was the discovery that RNA can act as a catalyst, which changed the perception of the role of RNA, that earned the Noble Prize for Professor Sidney Altman at Yale University and Professor Thomas Cech at the University of Colorado in 1989. The concept of a ribozyme, RNA that is able to catalyze its own replication and the synthesis of other RNA molecules, was proposed by these scientists. This led to an idea that RNA may be the first genetic material on earth, creating the concept of the “RNA world”. The property of RNA to act as both genes and enzymes could offer a solution to the “chicken-and-egg” problem, supporting the belief that the “RNA world” could be the original pathway to cells. This also suggested that RNA could play a more active role in gene expression than previously thought. A flurry of research activity in the field of RNA followed this discovery, and earned for RNA a pivotal position in cellular biology. Another breakthrough in RNA research was the discovery that small double-stranded RNA (dsRNA) could trigger silencing of a complementary messenger RNA sequence in the nematode Caenorhabditis elegans, a process termed “RNA interference” (RNAi). By use of artificial dsRNA, the RNAi mechanism was also shown to work in mammalian cells, opening up a new era in basic research and disease therapy. This work was honored in 2006 when Professor Andrew Z. Fire from Stanford University and Professor Craig C. Mello from the University of Massachusetts Medical School in Worcester received the Noble Prize for Medicine. The discovery of RNAi has added further complications to our understanding of gene regulation and, consequently, has created new opportunities in this research field. In the same year, the Noble Prize for Chemistry was awarded to Professor Roger D. Kornberg for determining how RNA molecules convert genetic information stored in DNA into working proteins. These two Noble awards in the same year have attracted much deserved attention to the field of RNA. RNAmolecules are now viewed in two different ways—as protein-coding RNAs and as noncoding RNAs. The small non-coding RNAs (<35 nucleotides in length) are classified into categories such as microRNAs (miRNAs), PIWIassociated RNAs, and small interfering RNAs (siRNAs), on the basis of their function, length, biogenesis, structural and/or sequence features, and protein-binding partners. Much scientific interest is now focused on the small noncoding RNAs, because they have been found to play a major role in gene expression. It is now well accepted that double-stranded small RNAs synthesized within the cell can alter and inhibit gene activity by RNAi-like mechanisms; this ultimately controls the development and physiological functions of cells and organisms. This discovery has had a tremendous impact on biomedical research and will ultimately lead to new therapies in medicine. In 2000 it was discovered that small nucleotidelength RNAs calledmicroRNAs (16–25 nucleotides in length) previously regarded as the dead matter of cells are regulators of gene expression. Deregulation in microRNA expression is now linked to a variety of diseases, most notably cancer. RNA, once regarded as merely a messenger molecule between DNA and protein, has now emerged as a promising target for Anal Bioanal Chem (2009) 394:1107–1108 DOI 10.1007/s00216-009-2778-9