Mapping of biological pathways regulated by microRNAs based on differential modulation of target gene expression level

• Grant number: 18/26409-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2019
• Effective date (End): December 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Danillo Pinhal
• Grantee: Lucas Alves da Costa Silva
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

In the last decades, a discovery of wide diversity of microRNAs - small endogenous non-coding RNAs - broadened horizons and revolutionized scientific knowledge regarding the mechanisms of regulation of gene expression in the metazoan genome. The ancestral origin of microRNAs, their dramatic expansion in bilateral animals, and their role in providing robustness to the transcription programs suggest that these molecules are protagonists in the evolution of the complexity of organism. Advances in understanding of microRNAs biology, coupled with the increasing availability of new genomes and sequenced transcripts, have revealed the molecular mechanisms underlying the evolution of miRNAs and their target genes. Furthermore, progress has also been achieved with respect to the evolution of regulatory networks containing miRNA and their association with the evolution of biological complexity itself. At the molecular level, the microRNA / target interaction is maintained by the Watson and Crick pairing of a small portion of the miRNA sequence to a complementary region in the target messenger RNA transcript. Such a peculiarity in pairing admits the occurrence of a broad spectrum of interactions, implying that a single miRNA can interact with multiple genes, and / or a single gene can be regulated by several miRNAs. The unraveling of true interactions has been obtained by functional studies (i.e., couple miRNAs/genes pairs to functions). These have also demonstrated the existence of patterns or modulating mechanisms in post-transcriptional gene regulation mediated by microRNAs and revealed clusters of functionally associated microRNAs that evolve in order to co-ordinate exert cooperative repressive effects on related target genes. Although modules have been detected as components of regulatory networks, however, the molecular mechanisms that support the modular organization of gene expression regulation and direct cooperative action among different microRNAs in different biological pathways remain unknown. Likewise, the potential association between the differential level of regulation/ modulation of targets and the different functions exerted by microRNAs needs to be rigorously tested. Thus, our hypothesis is that there is a complex and highly organized pattern in the cells regulating gene expression dependent on the intensity of repression of the microRNA on the target, and the mapping of which will allow the determination of interdependent regulatory circuits. This project aims to evaluate whether microRNAs regulate with similar intensities genes involved in related biological functions. For this, the in-depth detailed analysis of a broad set of global expression data of target messenger RNAs after perturbation of the expression of selected microRNAs is proposed. From this bioinformatic analysis it is expected to clarify the mechanisms underlying the functional activity of different target miRNA modules and their enrichment in distinct biological processes.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA, UR C.; BOVOLENTA, LUIZ A.; ALVES, LUCAS; FIGUEIREDO, LUCAS; RIBEIRO, AMANDA O.; CAMPOS, VINICIUS E.; LEMKE, NEY; PINHAL, DANILLO. Understanding the Modus Operandi of MicroRNA Regulatory Clusters. CELLS, v. 8, n. 9, SEP 2019. (18/05484-0, 18/26409-6, 12/13450-1, 12/15589-7, 15/19176-7, 17/17510-2)