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. 2004 Sep 8;32(16):4812-20.
doi: 10.1093/nar/gkh818. Print 2004.

Over 20% of human transcripts might form sense-antisense pairs

Jianjun Chen  1 , Miao Sun, W James Kent, Xiaoqiu Huang, Hanqing Xie, Wenquan Wang, Guolin Zhou, Run Zhang Shi, Janet D Rowley
Affiliations

Over 20% of human transcripts might form sense-antisense pairs

Jianjun Chen et al. Nucleic Acids Res. .

Abstract

The major challenge to identifying natural sense- antisense (SA) transcripts from public databases is how to determine the correct orientation for an expressed sequence, especially an expressed sequence tag sequence. In this study, we established a set of very stringent criteria to identify the correct orientation of each human transcript. We used these orientation-reliable transcripts to create 26 741 transcription clusters in the human genome. Our analysis shows that 22% (5880) of the human transcription clusters form SA pairs, higher than any previous estimates. Our orientation-specific RT-PCR results along with the comparison of experimental data from previous studies confirm that our SA data set is reliable. This study not only demonstrates that our criteria for the prediction of SA transcripts are efficient, but also provides additional convincing data to support the view that antisense transcription is quite pervasive in the human genome. In-depth analyses show that SA transcripts have some significant differences compared with other types of transcripts, with regard to chromosomal distribution and Gene Ontology-annotated categories of physiological roles, functions and spatial localizations of gene products.

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Figures

Figure 1
Figure 1
Classification of the transcription clusters in the human genome. (A) Eight categories and sub-categories of the transcription cluster are shown. The categories are classified according to the transcribed patterns of how the transcripts are mapped on the genome sequences. (B) The descriptions of each category are shown briefly. Total cluster counts as well as sequence number for each category are presented. ‘mRNA’, ‘Intron’ or ‘CDS’ refers to the number of the clusters which contain known mRNA(s), intron-spanning sequnce(s) that span at least one ‘consensus’ intron (flanked by consensus donor and acceptor splice sites) or protein-coding sequence(s), respectively.
Figure 2
Figure 2
Assessment of transcriptional directionality by orientation-specific RT–PCR. SA-1 to SA-25 are 25 randomly selected human SA candidates, and NC-1 to NC-10 are 10 negative controls (see Materials and Methods). A 1.5% agarose gel was used for RT–PCR product checking, and ‘1 kb Plus DNA Ladder’ (Invitrogen) was used as DNA molecular weight marker (M). For each candidate or negative control, four RT–PCR reactions were carried out (see Materials and Methods). All the positive controls were detected as positive and all the negative controls were detected as negative (data not shown). Except for SA-12, 24 out of the 25 SA candidate primer sets and no negative control primer sets were positive for antisense transcription over the regions queried. Of these 24 sets, 23 were also positive for sense transcription, except for SA-21. All the 10 negative controls were positive only for their sense transcription, not for antisense transcription. In addition, only one of the SA candidate genes (i.e. the antisense gene of the SA-6 pair; NM_002643) was included in Yelin et al.'s (14) micro-array data set; it was not detected by their micro-array, but was detected by our RT–PCR. In addition, sense gene (NM_003275) of the SA-15 and antisense gene (NM_032622) of the SA-17 were also included in Shendure and Church's (13) RT–PCR analysis, and both of them were detected as positive in both RT–PCR analyses.
Figure 3
Figure 3
Chromosome map of SA clusters and NOB clusters. All of the mapped positions of the bi-directional transcription clusters are represented schematically. The SA and NOB clusters (above and below) are in magenta and in blue, respectively. Note that SA and NOB clusters are widespread on every chromosome except for chromosomes X and Y; there are no SA clusters on the Y chromosome. Centromeres, the short arms of chromosomes 13, 14, 15, 21 and 22, the variable heterochromatic regions on chromosomes 1, 9 and 16, and the variable region at the q-terminus end of chromosome Y are essentially not sequenced and annotated (42). Thus, no SA or NOB loci are observed in these regions.
Figure 4
Figure 4
GO analysis. Because one gene (i.e. transcription cluster) might match several different GO terms, the sum of gene percentages of all sub-trees in a given ontology would be higher than 100%. (A) In molecular functions, SA genes have a significantly higher percentage participating in ‘translation regulator activity’ (1.6 versus 0.7%), but a significantly lower percentage in ‘signal transducer activity’ (16.7 versus 20.0%) than other genes. (B) In biological process, SA genes have a significantly higher percentage in ‘response to DNA damage stimulus’ (2.8 versus 1.9%) and ‘cell growth and/or maintenance’ (36.8 versus 32.0%), but a significantly lower percentage in ‘development’ (13.7 versus 16.4%), ‘transmission of nerve impulse’ (1.7 versus 2.9%), ‘response to external stimulus’ (9.6 versus 13.1%) and ‘immune response’ (4.6 versus 7.2%) than other genes. (C) In cellular component, SA genes have a significantly higher percentage in ‘nucleus’ (38.1 versus 33.9%) and ‘cytoplasm’ (36.0 versus 31.9%), but a significantly lower percentage in ‘extracellular’ (9.2 versus 11.8%) than other genes.
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