Abstract
For a significant fraction of mRNAs, their expression is regulated by other RNAs, including
cis
natural antisense transcripts (
cis
-NATs) that are complementary mRNAs transcribed from opposite strands of DNA at the same genomic locus. The regulatory mechanism of mRNA expression by
cis
-NATs is unknown, although a few possible explanations have been proposed. To understand this regulatory mechanism, we conducted a large-scale analysis of the currently available data and examined how the overlapping arrangements of
cis
-NATs affect their expression level. Here, we show that for both human and mouse the expression level of
cis
-NATs decreases as the length of the overlapping region increases. In particular, the proportions of the highly expressed
cis
-NATs in all
cis
-NATs examined were ∼36 and 47% for human and mouse, respectively, when the overlapping region was <200 bp. However, both proportions decreased to virtually zero when the overlapping regions were >2000 bp in length. Moreover, the distribution of the expression level of
cis
-NATs changes according to different types of the overlapping pattern of
cis
-NATs in the genome. These results are consistent with the transcriptional collision model for the regulatory mechanism of gene expression by
cis
-NATs.