Oliveira, Ur C.
Bovolenta, Luiz A.
Ribeiro, Amanda O.
Campos, Vinicius E.
Total Authors: 8
 Sao Paulo State Univ UNESP, Dept Genet, Inst Biosci Botucatu, BR-18618689 Sao Paulo, SP - Brazil
 Sao Paulo State Univ UNESP, Dept Phys & Biophys, BR-18618689 Sao Paulo, SP - Brazil
 Univ Fed Pelotas, Technol Dev Ctr, Lab Struct Genom GenEstrut, Grad Program Biotechnol, BR-96010610 Pelotas, RS - Brazil
Total Affiliations: 3
Web of Science Citations:
MicroRNAs (miRNAs) are non-coding RNAs that regulate a wide range of biological pathways by post-transcriptionally modulating gene expression levels. Given that even a single miRNA may simultaneously control several genes enrolled in multiple biological functions, one would expect that these tiny RNAs have the ability to properly sort among distinctive cellular processes to drive protein production. To test this hypothesis, we scrutinized previously published microarray datasets and clustered protein-coding gene expression profiles according to the intensity of fold-change levels caused by the exogenous transfection of 10 miRNAs (miR-1, miR-7, miR-9, miR-124, miR-128a, miR-132, miR-133a, miR-142, miR-148b, miR-181a) in a human cell line. Through an in silico functional enrichment analysis, we discovered non-randomic regulatory patterns, proper of each cluster identified. We demonstrated that miRNAs are capable of equivalently modulate the expression signatures of target genes in regulatory clusters according to the biological function they are assigned to. Moreover, target prediction analysis applied to ten vertebrate species, suggest that such miRNA regulatory modus operandi is evolutionarily conserved within vertebrates. Overall, we discovered a complex regulatory cluster-module strategy driven by miRNAs, which relies on the controlled intensity of the repression over distinct targets under specific biological contexts. Our discovery helps to clarify the mechanisms underlying the functional activity of miRNAs and makes it easier to take the fastest and most accurate path in the search for the functions of miRNAs in any distinct biological process of interest. (AU)