A highly expressed miR-101 isomiR is a functional silencing small RNA

BMC Genomics

Research Article

Eulàlia Martí¹  Mónica Bañez-Coronel¹  Xavier Estivill¹  Lorena Pantano²  Franc Llorens³  Jose Antonio del Río³  Isidre Ferrer⁴ 

[1] Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation (CRG) and UPF, Barcelona, Spain;Universitat Pompeu Fabra (UPF), Barcelona, Spain;Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, (CIBERESP), Barcelona, Spain;Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Spain;Molecular and Cellular Neurobiotechnology Group, Institut de Bioenginyeria de Catalunya (IBEC), Parc Científic de Barcelona, Barcelona, Spain;Department of Cell Biology, University of Barcelona (UB), Barcelona, Spain;Network Biomedical Research Center for Neurodegenerative Diseases (CIBERNED), Barcelona, Spain;Network Biomedical Research Center for Neurodegenerative Diseases (CIBERNED), Barcelona, Spain;Institut Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain;

关键词: MicroRNA;    miR-101;    IsomiR;    Ultra-sequencing;    Deep-sequencing;   

DOI  :  10.1186/1471-2164-14-104

 received in 2012-08-15, accepted in 2013-01-30,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101).ResultsThe analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101.ConclusionsThese results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.

【 授权许可】

Unknown   
© Llorens et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.