Understanding the Modus Operandi of MicroRNA Regulatory Clusters

Author(s)

Oliveira, Ur C. ^[1] ; Bovolenta, Luiz A. ^[2] ; Alves, Lucas ^[1] ; Figueiredo, Lucas ^[1] ; Ribeiro, Amanda O. ^[1] ; Campos, Vinicius E. ^[3] ; Lemke, Ney ^[2] ; Pinhal, Danillo ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Dept Genet, Inst Biosci Botucatu, BR-18618689 Sao Paulo, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Dept Phys & Biophys, BR-18618689 Sao Paulo, SP - Brazil

^[3] Univ Fed Pelotas, Technol Dev Ctr, Lab Struct Genom GenEstrut, Grad Program Biotechnol, BR-96010610 Pelotas, RS - Brazil

• Document type: Journal article
• Source: CELLS; v. 8, n. 9 SEP 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 18/05484-0 - Functional analysis of microRNAs on cellular dedifferentiation during tissue regeneration in the zebrafish model
• Grantee: Danillo Pinhal
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/26409-6 - Mapping of biological pathways regulated by microRNAs based on differential modulation of target gene expression level
• Grantee: Lucas Alves da Costa Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/13450-1 - Large scale exploratory analysis of Nile tilapia's miRNA expression using bioinformatics tools.
• Grantee: Luiz Augusto Bovolenta
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/15589-7 - Investigation of the composition, function and evolutionary dynamics of microRNAs in fish genomes using RNA-Seq and reverse genetics
• Grantee: Danillo Pinhal
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/19176-7 - Discovering variations and functions from non-coding Small RNAs in Oreochromis niloticus
• Grantee: Luiz Augusto Bovolenta
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 17/17510-2 - Investigation of the role of m6A methylation on microRNA biogenesis and arm-switching using zebrafish as biological model.
• Grantee: Arthur Casulli de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate