Widespread occurrence of antisense transcription in the human genome

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.

[1]  R. Stoughton,et al.  Experimental annotation of the human genome using microarray technology , 2001, Nature.

[2]  B. Bass,et al.  RNA editing and hypermutation by adenosine deamination. , 1997, Trends in biochemical sciences.

[3]  P. Murphy,et al.  Regulation of gene expression by natural antisense RNA transcripts , 1997, Neurochemistry International.

[4]  Madhur Kumar,et al.  Antisense RNA: Function and Fate of Duplex RNA in Cells of Higher Eukaryotes , 1998, Microbiology and Molecular Biology Reviews.

[5]  Jidong Liu,et al.  Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is induced by viral oncoproteins , 1998, Oncogene.

[6]  B. Bass Double-Stranded RNA as a Template for Gene Silencing , 2000, Cell.

[7]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[8]  R. Simons,et al.  Antisense RNA control in bacteria, phages, and plasmids. , 1994, Annual review of microbiology.

[9]  C. Vaquero,et al.  Do natural antisense transcripts make sense in eukaryotes? , 1998, Gene.

[10]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[11]  P. Rouzé,et al.  The sense of naturally transcribed antisense RNAs in plants. , 2000, Trends in plant science.

[12]  D J Lipman,et al.  Making (anti)sense of non-coding sequence conservation. , 1997, Nucleic acids research.

[13]  M. Lazar,et al.  Post-transcriptional Regulation of Thyroid Hormone Receptor Expression by cis-Acting Sequences and a Naturally Occurring Antisense RNA* , 2000, The Journal of Biological Chemistry.

[14]  Avi Shoshan,et al.  Large-scale protein annotation through gene ontology. , 2002, Genome research.

[15]  W. Reith,et al.  Cyclin E2: a novel CDK2 partner in the late G1 and S phases of the mammalian cell cycle , 1998, Oncogene.

[16]  R. Lyle,et al.  The uniqueness of the imprinting mechanism. , 2000, Current opinion in genetics & development.

[17]  D. Higgins,et al.  Overlapping Antisense Transcription in the Human Genome , 2002, Comparative and functional genomics.

[18]  S. Fields,et al.  Two cellular proteins that bind to wild-type but not mutant p53. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Phillip D Zamore,et al.  Ancient Pathways Programmed by Small RNAs , 2002, Science.

[20]  L. Duret,et al.  Strong conservation of non-coding sequences during vertebrates evolution: potential involvement in post-transcriptional regulation of gene expression. , 1993, Nucleic acids research.

[21]  P. Ferrara,et al.  HUMAN 76P : A NEW MEMBER OF THE GAMMA -TUBULIN-ASSOCIATED PROTEIN FAMILY , 1999 .

[22]  Yudong D. He,et al.  Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer , 2001, Nature Biotechnology.

[23]  C. Gissi,et al.  Structural and functional features of eukaryotic mRNA untranslated regions. , 2001, Gene.

[24]  R. Kelley,et al.  Noncoding RNA Genes in Dosage Compensation and Imprinting , 2000, Cell.

[25]  Jay Shendure,et al.  Computational discovery of sense-antisense transcription in the human and mouse genomes , 2002, Genome Biology.

[26]  P. Murphy,et al.  Expression of alternatively spliced FGF-2 antisense RNA transcripts in the central nervous system: regulation of FGF-2 mRNA translation , 2000, Molecular and Cellular Endocrinology.

[27]  Kei-Hoi Cheung,et al.  An integrated approach for finding overlooked genes in yeast , 2002, Nature Biotechnology.

[28]  Steven E. Rokita,et al.  Natural antisense RNA/target RNA interactions: Possible models for antisense oligonucleotide drug design , 1997, Nature Biotechnology.

[29]  Ben Lehner,et al.  Antisense transcripts in the human genome. , 2002, Trends in genetics : TIG.