J. theor. Biol. (1982) 98, 563-574 RNA Splicing: Advantages of Parallel Processing GUNNARVONHEIJNE Research Group for Theoretical Biophysics, Department of Theoretical Physics, Royal Institute of Technology, S- 100 44 Stockholm, Sweden AND MICHAEL A. SAVAGEAU Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, U.S.A. (Received 15 March 1982) Parallel and sequential modes of RNA processing are systematically com- pared by an analysis of the relevant kinetic reaction schemes. The parallel mode is shown to be superior in the sense that it allows molecules to be processed with larger numbers of introns, smaller losses of immature intermediates, and shorter processing times. It also is more sensitive to variations in the rate constants for individual splice-reactions, and hence more amenable to evolutionary refinements. Quantitatively, the parallel mode agrees well with published experimental data. Introduction Processing of ribonucleic acid provides an example of a general class of biochemical reactions in which a large molecule is modified at a number of different sites during its maturation. If the sites to be modified are far apart in the molecular structure, one may reasonably expect them to be attacked independently, either by the same of different enzymes. Alterna- tively, a strictly sequential mode of processing is possible, in which site A must be modified before site B can be attacked, and so on. Of course, various hybrid schemes also can be envisioned. Splicing of eukaryotic RNA, in which the introns to be removed are usually separated by exons a few hundred nucleotides long, would seem a priori likely to conform to the first processing mode, and some fairly recent experimental data indicate that this might be true in many cases (Chow, Broker & Lewis, 1979; Ryffel et al., 1980; Tsai et al., 1980). However, no detailed analysis of the parallel reaction scheme has yet been applied to these data, and their interpretation has remained rather qualitative. 563 0022-5193/82/200563+12$03.00/0 @ 1982 Academic Press Inc. (London) Ltd.