RNA processing comes of age

Abstract

During the past two decades, an awareness of the importance of RNA processing has evolved as part of the quest to understand how living cells express the information encoded in their genes. As the knowledge of gene expression has expanded, we have come to realize that the old central dogma of DNA → RNA → protein is embellished with elegant and intricate design features, many of which are revealed in the processing of primary gene transcripts into the functional forms of RNA. The production of the two large structural RNA components of the ribosome (rRNAs), the synthesis of transfer RNA (tRNA), and the formation of messenger RNA (mRNA) in higher organisms all involve rather elaborate processing reactions, including nucleolytic cleavages, ligations, terminal additions, and nucleoside modifications. A raison d'etre for processing is readily apparent in the case of the coordinate production of rRNA components from a single transcriptional unit and the synthesis of mRNA from noncontiguous genetic elements. However, the purpose of the polyadenylate and methylated cap structures that are added to the termini of mRNA and the modification of internal nucleotides in most RNA species is less clear. These structural alterations may serve to improve the stability of the RNA and the efficiency of its function, but they might also be implicated in more subtle forms of discriminative regulation that are yet to be discovered. In any event, it is clear that RNA processing constitutes a major cellular activity and an integral part of the mechanism of gene expression. In this essay the author tries to trace the evolution of our concepts of RNA processing in relation to the contemporary issues of cellular and molecular biology and to the introduction of key experimental tools which were critical to the development of these concepts.