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Widespread occurrence of antisense transcription in the human genome

Abstract

An increasing number of eukaryotic genes are being found to have naturally occurring antisense transcripts. Here we study the extent of antisense transcription in the human genome by analyzing the public databases of expressed sequences using a set of computational tools designed to identify sense-antisense transcriptional units on opposite DNA strands of the same genomic locus. The resulting data set of 2,667 sense-antisense pairs was evaluated by microarrays containing strand-specific oligonucleotide probes derived from the region of overlap. Verification of specific cases by northern blot analysis with strand-specific riboprobes proved transcription from both DNA strands. We conclude that ≥60% of this data set, or 1,600 predicted sense-antisense transcriptional units, are transcribed from both DNA strands. This indicates that the occurrence of antisense transcription, usually regarded as infrequent, is a very common phenomenon in the human genome. Therefore, antisense modulation of gene expression in human cells may be a common regulatory mechanism.

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Figure 1: Schematic representation of the sources of information that can be used to deduce the DNA strand from which an expressed sequence is derived.
Figure 2: Validation of sense-antisense pairs by northern blot analysis.
Figure 3: Analysis of the overlap region between the transcriptional units of TP53BP1 and 76P.
Figure 4: Analysis of the overlap region between the transcriptional units of CCNE2 and FLJ20530.

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Acknowledgements

We want to thank Alon Wasserman and Brian Meloon for their critical help with the Antisensor design and analysis of microarray results; Mervi Heiskanen, Ruth Goldin, and Paul Nisson for their valuable assistance in the setup of the microarray methodology; Han Xie for the GO engine analysis; Dan Sztybel for technical help; Raveh Gill-More, Gady Cojocaru, Naftali Kaminski, and Gidi Rechavi for critical reading of the manuscript and helpful discussions; Sarah Pollock for her innovative ideas, and Salomon Langer for his inspirational support.

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Correspondence to Galit Rotman.

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The authors are or were employees of Compugen Ltd., which has a patent application pending.

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Yelin, R., Dahary, D., Sorek, R. et al. Widespread occurrence of antisense transcription in the human genome. Nat Biotechnol 21, 379–386 (2003). https://doi.org/10.1038/nbt808

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