MicroRNA Screening and the Quest for Biologically Relevant Targets

Ana Eulalio; Miguel Mano

doi:10.1177/1087057115578837

MicroRNA Screening and the Quest for Biologically Relevant Targets

Ana Eulalio, Miguel Mano^*

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that post-transcriptionally regulate gene expression by repressing target transcripts containing partially or fully complementary binding sites. Despite their relatively low number, miRNAs have been shown to directly regulate a large fraction of the transcriptome. In agreement with their pervasive role in the regulation of eukaryotic gene expression, miRNAs have been implicated in virtually all biological processes, including different pathologies. The use of screening technologies to systematically analyze miRNA function in cell-based assays offers a unique opportunity to gain new insights into complex biological and disease-relevant processes. Given the low complexity of the miRNome and the similarities to small interfering RNA (siRNA) screening experimental approaches, phenotypic screening using genome-wide libraries of miRNA mimics or inhibitors is not, per se, technically challenging. The identification of miRNA targets and, more importantly, the characterization of their mechanisms of action through the identification of the key targets underlying observed phenotypes remain the major challenges of this approach. This article provides an overview of cell-based screenings for miRNA function that were performed in different biological contexts. The advantages and limitations of computational and experimental approaches commonly used to identify miRNA targets are also discussed.

Original language	English
Pages (from-to)	1003-1017
Number of pages	15
Journal	JOURNAL OF BIOMOLECULAR SCREENING
Volume	20
Issue number	8
DOIs	https://doi.org/10.1177/1087057115578837
Publication status	Published - 24 Sept 2015

Keywords

high-throughput screening
microRNA
miRNA screening
miRNA target identification

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title = "MicroRNA Screening and the Quest for Biologically Relevant Targets",

abstract = "MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that post-transcriptionally regulate gene expression by repressing target transcripts containing partially or fully complementary binding sites. Despite their relatively low number, miRNAs have been shown to directly regulate a large fraction of the transcriptome. In agreement with their pervasive role in the regulation of eukaryotic gene expression, miRNAs have been implicated in virtually all biological processes, including different pathologies. The use of screening technologies to systematically analyze miRNA function in cell-based assays offers a unique opportunity to gain new insights into complex biological and disease-relevant processes. Given the low complexity of the miRNome and the similarities to small interfering RNA (siRNA) screening experimental approaches, phenotypic screening using genome-wide libraries of miRNA mimics or inhibitors is not, per se, technically challenging. The identification of miRNA targets and, more importantly, the characterization of their mechanisms of action through the identification of the key targets underlying observed phenotypes remain the major challenges of this approach. This article provides an overview of cell-based screenings for miRNA function that were performed in different biological contexts. The advantages and limitations of computational and experimental approaches commonly used to identify miRNA targets are also discussed.",

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author = "Ana Eulalio and Miguel Mano",

note = "Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: MM is supported by the FIRB RBAP11Z4Z9 project from the Ministero dell{\textquoteright}Istruzione, dell{\textquoteright}Universit{\`a} e della Ricerca (MIUR), Italy, and the FCT Investigator Programme IF/00694/2013 from the Portuguese Foundation for Science and Technology (FCT), Portugal. AE is supported by the Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Research Network (BioSysNet) and DFG project BR 4837/1-1, Germany. Publisher Copyright: {\textcopyright} 2015 Society for Laboratory Automation and Screening.",

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N1 - Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: MM is supported by the FIRB RBAP11Z4Z9 project from the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Italy, and the FCT Investigator Programme IF/00694/2013 from the Portuguese Foundation for Science and Technology (FCT), Portugal. AE is supported by the Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Research Network (BioSysNet) and DFG project BR 4837/1-1, Germany. Publisher Copyright: © 2015 Society for Laboratory Automation and Screening.

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N2 - MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that post-transcriptionally regulate gene expression by repressing target transcripts containing partially or fully complementary binding sites. Despite their relatively low number, miRNAs have been shown to directly regulate a large fraction of the transcriptome. In agreement with their pervasive role in the regulation of eukaryotic gene expression, miRNAs have been implicated in virtually all biological processes, including different pathologies. The use of screening technologies to systematically analyze miRNA function in cell-based assays offers a unique opportunity to gain new insights into complex biological and disease-relevant processes. Given the low complexity of the miRNome and the similarities to small interfering RNA (siRNA) screening experimental approaches, phenotypic screening using genome-wide libraries of miRNA mimics or inhibitors is not, per se, technically challenging. The identification of miRNA targets and, more importantly, the characterization of their mechanisms of action through the identification of the key targets underlying observed phenotypes remain the major challenges of this approach. This article provides an overview of cell-based screenings for miRNA function that were performed in different biological contexts. The advantages and limitations of computational and experimental approaches commonly used to identify miRNA targets are also discussed.

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MicroRNA Screening and the Quest for Biologically Relevant Targets

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