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Nucleic Acids Research, 1988, Vol. 16, No. 22 10849-10860
© 1988

MOLECULAR BIOLOGY

Differential premature termination of transcription as a proposed mechanism for the regulation of coronavirus gene expression

D.A.M. Konings, P.J. Bredenbeek1, J.F.H. Noten1, P. Hogeweg2 and W.J.M. Spaan1

European Molecular Biology Laboratory Postfach 10.2209, 6900 Heidelberg, FRG 1Institute of Virology, Department of Infectious Diseases and Immunology Yalelaan 1 2Bioinformatics Group, Padualaan 8, University of Utrecht Utrecht, The Netherlands

Received August 2, 1988. Revised September 29, 1988. Accepted October 21, 1988.

We propose that the different subgenomic mRNA levels of coronaviruses are controlled through differential premature termination of transcription, and are modulated by the relative strength of transcnptional initiation/blockage events. We present the complete Bet of sequences covering the leader encoding and intergenic regions of the MHV-A59 strain. A computer-assisted analysis of the two now complete sets of these sequences of strain IBV-M42 and MHV-A59 shows that, in contrast to the previous theory, differences amongst stabilities of intermolecular base-pairings between the leader and the intergenic regions are not sufficient to determine the mRNA gradients in both MHV and IBV infected cells. Neither can the accessibility of the interacting regions on the leader and the negative stranded genome, as revealed by secondary structure analysis, explain the mRNA levels. The nested gene organisation itself, on the other hand, could be responsible for observed mRNA levels gradually increasing with gene order. Relatively slow new initiation events at intergenic regions are proposed to block elongation of passing transcripts which, via temporary pausing, can cause premature termination of transcription. This effects longer transcripts more than shorter ones.


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