Alternative mRNA fates identified in microRNA-associated transcriptome analysis

• Published in: BMC genomics Vol. 13; no. 1; p. 561
• Main Authors: Carroll, Adam P, Tran, Nham, Tooney, Paul A, Cairns, Murray J
• Format: Journal Article
• Language: English
• Published: London BioMed Central 19.10.2012; BioMed Central Ltd; Springer Nature B.V; BMC
• Subjects: Algorithms; Analysis; Animal Genetics and Genomics; Binding Sites; Biomedical and Life Sciences; Cell adhesion & migration; Cell cycle; Cell Line, Tumor; Cell Lineage - genetics; Cells; Cytokines; E2F1; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Gene expression; Gene Expression Profiling; Gene silencing; Genes; Genetic aspects; Genetic transcription; Genetic translation; Genomes; Genomics; HEK293 Cells; HeLa Cells; Human and rodent genomic; Humans; Kinases; Life Sciences; Messenger RNA; Microarrays; Microbial Genetics and Genomics; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miR-181b; miRNA; Nucleic acids; Physiological aspects; Plant Genetics and Genomics; Proteomics; Research Article; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Schizophrenia; Studies; Target identification; Australia; E2F1; miRNA; miR-181b; Gene expression; Target identification
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/1471-2164-13-561

Background MicroRNA (miRNA) are small non-coding RNA molecules which function as nucleic acid-based specificity factors in the universal RNA binding complex known as the RNA induced silencing complex (RISC). In the canonical gene-silencing pathway, these activated RISC particles are associated with RNA decay and gene suppression, however, there is evidence to suggest that in some circumstances they may also stabilise their target RNA and even enhance translation. To further explore the role of miRNA in this context, we performed a genome-wide expression analysis to investigate the molecular consequences of bidirectional modulation of the disease-associated miRNAs miR-181b and miR-107 in multiple human cell lines. Results This data was subjected to pathways analysis and correlated against miRNA targets predicted through seed region homology. This revealed a large number of both conserved and non-conserved miRNA target genes, a selection of which were functionally validated through reporter gene assays. Contrary to expectation we also identified a significant proportion of predicted target genes with both conserved and non-conserved recognition elements that were positively correlated with the modulated miRNA. Finally, a large proportion of miR-181b associated genes devoid of the corresponding miRNA recognition element, were enriched with binding motifs for the E2F1 transcription factor, which is encoded by a miR-181b target gene. Conclusions These findings suggest that miRNA regulate target genes directly through interactions with both conserved and non-conserved target recognition elements, and can lead to both a decrease and increase in transcript abundance. They also multiply their influence through interaction with transcription factor genes exemplified by the observed miR-181b/E2F1 relationship.