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Trans-natural antisense transcripts including noncoding RNAs in 10 species: implications for expression regulation.

ABSTRACT: Natural antisense transcripts are at least partially complementary to their sense transcripts. Cis-Sense/Antisense pairs (cis-SAs) have been extensively characterized and known to play diverse regulatory roles, whereas trans-Sense/Antisense pairs (trans-SAs) in animals are poorly studied. We identified long trans-SAs in human and nine other animals, using ESTs to increase coverage significantly over previous studies. The percentage of transcriptional units (TUs) involved in trans-SAs among all TUs was as high as 4.13%. Particularly 2896 human TUs (or 2.89% of all human TUs) were involved in 3327 trans-SAs. Sequence complementarities over multiple segments with predicted RNA hybridization indicated that some trans-SAs might have sophisticated RNA-RNA pairing patterns. One-fourth of human trans-SAs involved noncoding TUs, suggesting that many noncoding RNAs may function by a trans-acting antisense mechanism. TUs in trans-SAs were statistically significantly enriched in nucleic acid binding, ion/protein binding and transport and signal transduction functions and pathways; a significant number of human trans-SAs showed concordant or reciprocal expression pattern; a significant number of human trans-SAs were conserved in mouse. This evidence suggests important regulatory functions of trans-SAs. In 30 cases, trans-SAs were related to cis-SAs through paralogues, suggesting a possible mechanism for the origin of trans-SAs. All trans-SAs are available at http://trans.cbi.pku.edu.cn/.

SUBMITTER: Li JT

PROVIDER: S-EPMC2528163 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Trans-natural antisense transcripts including noncoding RNAs in 10 species: implications for expression regulation.

Li Jiong-Tang JT Zhang Yong Y Kong Lei L Liu Qing-Rong QR Wei Liping L

Nucleic acids research 20080724 15

Natural antisense transcripts are at least partially complementary to their sense transcripts. Cis-Sense/Antisense pairs (cis-SAs) have been extensively characterized and known to play diverse regulatory roles, whereas trans-Sense/Antisense pairs (trans-SAs) in animals are poorly studied. We identified long trans-SAs in human and nine other animals, using ESTs to increase coverage significantly over previous studies. The percentage of transcriptional units (TUs) involved in trans-SAs among all T ...[more]

PMID: 18653530

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Project description:BackgroundIn spite of large intergenic spaces in plant and animal genomes, 7% to 30% of genes in the genomes encode overlapping cis-natural antisense transcripts (cis-NATs). The widespread occurrence of cis-NATs suggests an evolutionary advantage for this type of genomic arrangement. Experimental evidence for the regulation of two cis-NAT gene pairs by natural antisense transcripts-generated small interfering RNAs (nat-siRNAs) via the RNA interference (RNAi) pathway has been reported in Arabidopsis. However, the extent of siRNA-mediated regulation of cis-NAT genes is still unclear in any genome.ResultsThe hallmarks of RNAi regulation of NATs are 1) inverse regulation of two genes in a cis-NAT pair by environmental and developmental cues and 2) generation of siRNAs by cis-NAT genes. We examined Arabidopsis transcript profiling data from public microarray databases to identify cis-NAT pairs whose sense and antisense transcripts show opposite expression changes. A subset of the cis-NAT genes displayed negatively correlated expression profiles as well as inverse differential expression changes under at least one of the examined developmental stages or treatment conditions. By searching the Arabidopsis Small RNA Project (ASRP) and Massively Parallel Signature Sequencing (MPSS) small RNA databases as well as our stress-treated small RNA dataset, we found small RNAs that matched at least one gene in 646 pairs out of 1008 (64%) protein-coding cis-NAT pairs, which suggests that siRNAs may regulate the expression of many cis-NAT genes. 209 putative siRNAs have the potential to target more than one gene and half of these small RNAs could target multiple members of a gene family. Furthermore, the majority of the putative siRNAs within the overlapping regions tend to target only one transcript of a given NAT pair, which is consistent with our previous finding on salt- and bacteria-induced nat-siRNAs. In addition, we found that genes encoding plastid- or mitochondrion-targeted proteins are over-represented in the Arabidopsis cis-NATs and that 19% of sense and antisense partner genes of cis-NATs share at least one common Gene Ontology term, which suggests that they encode proteins with possible functional connection.ConclusionThe negatively correlated expression patterns of sense and antisense genes as well as the presence of siRNAs in many of the cis-NATs suggest that siRNA regulation of cis-NATs via the RNAi pathway is an important gene regulatory mechanism for at least a subgroup of cis-NATs in Arabidopsis.

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Trans-natural antisense transcripts including noncoding RNAs in 10 species: implications for expression regulation.

Publications

Trans-natural antisense transcripts including noncoding RNAs in 10 species: implications for expression regulation.

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