Originally published as Genetics Published Articles Ahead of Print on April 3, 2007.

Genetics, Vol. 176, 1299-1306, June 2007, Copyright © 2007
doi:10.1534/genetics.106.069484

Transcriptional Interferences in cis Natural Antisense Transcripts of Humans and Mice

Naoki Osato, Yoshiyuki Suzuki, Kazuho Ikeo and Takashi Gojobori1

Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Research Organization of Information and Systems, Mishima 411-8540, Japan

1 Corresponding author: Center for Information Biology and DNA Data Bank of Japan, National Institutes of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
E-mail: tgojobor{at}genes.nig.ac.jp

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.