Alternative mRNA fates identified in microRNA-associated transcriptome analysis.
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.
School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
Adam P
AP
Carroll
Nham
N
Tran
Paul A
PA
Tooney
Murray J
MJ
Cairns
D001665:Binding Sites; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D050687:E2F1 Transcription Factor; D035683:MicroRNAs; D012333:RNA, Messenger