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

Franc Llorens, Mónica Bañez-Coronel, Lorena Pantano, Jose Antonio del Río, Isidre Ferrer, Xavier P. Estivill, Eulàlia Martí

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background: MicroRNAs (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).Results: The 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.Conclusions: These 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.

Original languageEnglish
Article number104
JournalBMC Genomics
Volume14
Issue number1
DOIs
Publication statusPublished - 15 Feb 2013
Externally publishedYes

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RNA Interference
MicroRNAs
Gene Expression
RNA Sequence Analysis
Untranslated RNA
Messenger RNA
Brain
Gene Silencing
Technology
Cell Line
Proteins

Keywords

  • Deep-sequencing
  • IsomiR
  • MicroRNA
  • miR-101
  • Ultra-sequencing

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Llorens, F., Bañez-Coronel, M., Pantano, L., del Río, J. A., Ferrer, I., Estivill, X. P., & Martí, E. (2013). A highly expressed miR-101 isomiR is a functional silencing small RNA. BMC Genomics, 14(1), [104]. https://doi.org/10.1186/1471-2164-14-104

A highly expressed miR-101 isomiR is a functional silencing small RNA. / Llorens, Franc; Bañez-Coronel, Mónica; Pantano, Lorena; del Río, Jose Antonio; Ferrer, Isidre; Estivill, Xavier P.; Martí, Eulàlia.

In: BMC Genomics, Vol. 14, No. 1, 104, 15.02.2013.

Research output: Contribution to journalArticle

Llorens, F, Bañez-Coronel, M, Pantano, L, del Río, JA, Ferrer, I, Estivill, XP & Martí, E 2013, 'A highly expressed miR-101 isomiR is a functional silencing small RNA', BMC Genomics, vol. 14, no. 1, 104. https://doi.org/10.1186/1471-2164-14-104
Llorens F, Bañez-Coronel M, Pantano L, del Río JA, Ferrer I, Estivill XP et al. A highly expressed miR-101 isomiR is a functional silencing small RNA. BMC Genomics. 2013 Feb 15;14(1). 104. https://doi.org/10.1186/1471-2164-14-104
Llorens, Franc ; Bañez-Coronel, Mónica ; Pantano, Lorena ; del Río, Jose Antonio ; Ferrer, Isidre ; Estivill, Xavier P. ; Martí, Eulàlia. / A highly expressed miR-101 isomiR is a functional silencing small RNA. In: BMC Genomics. 2013 ; Vol. 14, No. 1.
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AB - Background: MicroRNAs (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).Results: The 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.Conclusions: These 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.

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