DO NATURAL ANTISENSE TRANSCRIPTS MAKE SENSE IN EUKARYOTES

The existence of naturally occurring antisense RNAs has been illustrat ed, in eukaryotes, by an increasing number of reports. The following r eview presents the major findings in this field, with a special focus on the regulation of gene expression exerted by endogenous complementa ry transcripts. A large variety of eukaryotic organisms, contains anti sense transcripts. Moreover, the great diversity of genetic loci encod ing overlapping sense and antisense RNAs suggests that such transcript s may be involved in numerous biological functions, such as control of development, adaptative response, viral infection. The regulation of gene expression by endogenous antisense RNAs seems of general importan ce in eukaryotes as already established in prokaryotes: it is likely t o be involved in the control of various biological functions and to pl ay a role in the development of pathological situations. Several exper imental evidences for coupled, balanced or unbalanced expression of se nse and antisense RNAs suggest that antisense transcripts may govern t he expression of their sense counterparts. Furthermore, documented exa mples indicate that this control may be exerted at many levels of gene expression (transcription, maturation, transport, stability and trans lation). This review also addresses the underlying molecular mechanism s of antisense regulation and presents the current mechanistic hypothe ses. (C) 1998 Elsevier Science B.V. All rights reserved.