Integrative analysis of the human cis -antisense gene pairs, miRNAs and their transcription regulation patterns

Abstract

Cis-antisense gene pairs (CASGPs) can transcribe mRNAs from an opposite strand of a given locus. To classify and understand diverse CASGP phenomena in the human we compiled a genome-wide catalog of CASGPs and integrated these sequences with microarray, SAGE and miRNA data. Using the concept of overlapping regions and clustering of SA transcripts by chromosome coordinates, we identified up to 9000 overlapping antisense loci. Four thousand three hundred and seventy-four of these CASGPs form 1759 complex gene architectures. We found that ∼35% (6347/18160) of RefSeq genes are overlapped with the antisense transcripts. About 30% of Affymetrix U133 microarray initial sequences map transcripts of ∼35% CASGPs and reveal mostly concordant expression in CASGPs. We found strong significant overrepresentation of human miRNA genes in loci of CASGPs. We developed a data-driven model of cross-talk between co-expressed CASGPs and DICER1-mediated miRNA pathway in normal spermatogenesis and in severe teratozoospermia. Specifically, we revealed complex SA structural–functional gene module composing the protein-coding genes, WDR6, DALRD3, NDUFAF3 and ncRNA precursors, mir-425 and mir-191, which could provide downregulation of ncRNA pathway via direct targeting DICER1 and basonuclin 2 transcripts by mir-425 and mir-191 in normal spermatogenesis, but this mechanism is switched off in severe teratozoospermia. The database is available from http://globalisland.bii.a-star.edu.sg/∼jiangtao/sas/index3.php?link =about

Transcriptome interrogation of human myometrium identifies differentially expressed sense-antisense pairs of protein-coding and long non-coding RNA genes in spontaneous labor at term

“…We assembled 18,498 experimentally supported [with full-length cDNA or manually-curated high-quality expressed sequence tag (EST) evidence], non-redundant (with respect to genomic position and orientation) lncRNA genes from multiple public sources: Gencode v3 [52] and v7 lncRNAs [38]; the human lncRNA catalog from our previous work [33]; NCBI Refseq non-coding transcripts; all human ESTs submitted to Genbank by RIKEN, Japan; manually annotated lncRNAs from human sense-antisense pairs [53,54]; and Broad Institute lincRNAs [35]. We used genomic positional overlap of UCSC all_mrna, all_est, and ref_all files from http://genome.ucsc.edu [55] as well as Gencode transcripts from www.gencodegenes.org [52,56] to define transcriptional unit boundaries according to the FANTOM3 definition of a transcriptional unit [57] along the hg19 assembly, in the UCSC Genome Brower (http://genome.ucsc.edu) [58], collapsing the cDNA/EST/Gencode/Broad transcript-to-genome alignments into genomic positionally nonredundant transcriptional units with one randomly selected reference transcript per transcriptional unit.…”

MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia

“…Functional transcripts using the opposite strands of the same genomic sequence have been reported: for example, EIF2A and SERP1 on chromosome 3, CDSN and PSORS1C1 on chromosome 3, and TIMP3 and SYN3 on chromosome 22. The expression patterns of these "gene pairs" usually show negative correlations, probably because of regulatory effects and the possibility of forming unstable double-stranded RNA from the primary transcripts (29,30). Lower miR-181a levels should then imply higher NR6A1 mRNA and protein levels and a higher transcription rate of the NR6A1 gene.…”

Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics

“…In both humans and the mouse, up to 70% of genomic loci exhibit evidence of transcription from the antisense strand as well as the sense strand [Grinchuk et al, 2010;Katayama et al, 2005;Werner et al, 2009]. These naturally occurring antisense transcripts may modulate the level of expression of their associated sense transcripts (or otherwise influence their processing) thereby adding another level of complexity to the regulation of gene expression [Faghihi and Wahlestedt, 2009;He et al, 2008].…”