Abstract
It has been realized in recent years that non-coding RNAs are playing important roles in genome functions and human diseases. Here we developed a new technology and observed a new pattern of gene expression. We observed that over 72% of RNAs in human genome are expressed in forward-reverse pairs, just like mirror images of each other between forward expression and reverse expression; the overview showed that it cannot be simply described as transcript overlapping, so we designated it as mirror expression. Furthermore, we found that the mirror expression is gene-specific and tissue-specific, and less common in the proximal promoter regions. The size of the shadows varies between different genes, different tissues and different classes. The shadow expression is most significant in the Alu element, it was also observed among L1, Simple Repeats and LTR elements, but rare in other repeats such as low-complexity, LINE/L2, DNA and MIRs. Although there is no evidence yet about the relationship of this mirror pattern and double-strand RNA (dsRNA), this new striking pattern provides a new clue and a new direction to unveil the role of RNAs in the genome functions and diseases.
Highlights
IntroductionHumans[7], but relatively little is known about their roles in eukaryotes[8]. Cis-natural antisense transcripts (NATs) may function through transcriptional regulation, alternative splicing, RNA duplex formation, double-strand RNA (dsRNA), RNA editing and RNBA interference (RNAi), DNA methylation, genomic imprinting, and X-chromosome inactivation[9,10,11]
Many non-coding transcripts overlap with known genes in antisense orientation, which is known as natural antisense transcripts (NATs)[1,2,3,4,5]
We further calculated the statistics how many mirror RNAs were present in multiple tissues, we found that as many as 72% of mirror RNAs are present in all 8 tissues (Fig. 5), indicating that most of the mirror RNAs are consistently present across many tissues instead of being specific in a particular tissue
Summary
Humans[7], but relatively little is known about their roles in eukaryotes[8]. Cis-NATs may function through transcriptional regulation, alternative splicing, RNA duplex formation, double-strand RNA (dsRNA), RNA editing and RNBA interference (RNAi), DNA methylation, genomic imprinting, and X-chromosome inactivation[9,10,11]. We developed a customized designed method to identify the sense and antisense transcripts and found the “mirror” pattern, in which a large number of expression signals are paired as mirrors or mirror images of each other. It addition, most of current reports on cis-NATs were focused on the NATs that overlap with known genes on their introns, exons, promoters, enhancers, untranslated regions (UTRs) and flanking sequences[7], NATs have not been well studied on the repetitive elements. By including the information on the repeats, we found that NATs are significantly much more widespread than current estimates in human tissues
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