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Title:
A highly expressed miR-101 isomiR is a functional silencing small RNA | BMC Genomics
Description:
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 5â or 3â 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 5â-trimming variant (5â-isomiR-101). Results The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5â-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5â-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5â-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5â-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 5â-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5â-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 5â-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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Keywords {đ}
isomir, pubmed, expression, article, google, scholar, mirna, human, cas, variants, ago, cells, central, figure, rna, gene, cell, genes, isomirs, microrna, shsyy, data, targets, control, sequence, transfected, brain, seed, expressed, sequencing, mrna, levels, sequences, file, analysis, risc, silencing, ezh, mirnas, target, samples, abundant, small, number, trimming, cancer, sample, shown, additional, total,
Topics {âïž}
de/apps/zmf/mirwalk/index increased bace1/beta-secretase expression open access article pri-mirna post-transcriptional editing microrna cluster mir-29a/b-1 article download pdf joint genome-wide profiling sh-sy5y neuroblastoma cells cold phosphate-buffered saline high-throughput sequencing technologies hif-1alpha/hif-1beta mouse nih-3t3 cells small-rna sequencing datasets 3â-biotin-5â-isomir-101 versus 3â-biotin-mir-101 differentiated sh-sy5y cells anti-flag antibody shows sh-sy5y cells decreased specific rt-qpcr assays negative post-transcriptional regulators rna-induced silencing complex high-throughput sequencing data sh-sy5y-ago2-flag transfected sh-sy5y cells sh-sy5y cells transfected nyap2 expression anti-correlated scn3b expression anti-correlated candidate age-related genes modulating age-related genes d-ago2 crossing thresholds mir-101-sequence-gene pair predicted polymerase activation/denaturation cycle deserves specific research de hoon mj ja del rĂo specific rt-qpcrs determinations eulĂ lia martĂ article llorens mirna/mrna binding leads micrornas en route ja de rĂo small rnas datasets isomir-dependent differential output control d-ago2 antibody xavier estivill coding regulatory rnas reveals argonaute association sh-sy5y cells privacy choices/manage cookies amyloid precursor protein universitat de barcelona
Questions {â}
- Filipowicz W, Bhattacharyya SN, Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
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headline:A highly expressed miR-101 isomiR is a functional silencing small RNA
description: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 5â or 3â 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 5â-trimming variant (5â-isomiR-101). The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5â-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5â-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5â-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5â-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 5â-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5â-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 5â-isomiR-101. 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.
datePublished:2013-02-15T00:00:00Z
dateModified:2013-02-15T00:00:00Z
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keywords:
MicroRNA
miR-101
IsomiR
Ultra-sequencing
Deep-sequencing
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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headline:A highly expressed miR-101 isomiR is a functional silencing small RNA
description: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 5â or 3â 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 5â-trimming variant (5â-isomiR-101). The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5â-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5â-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5â-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5â-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 5â-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5â-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 5â-isomiR-101. 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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MicroRNA
miR-101
IsomiR
Ultra-sequencing
Deep-sequencing
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP)
address:
name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP), Barcelona, Spain
type:PostalAddress
type:Organization
email:[email protected]
name:EulĂ lia MartĂ
affiliation:
name:Centre for Genomic Regulation (CRG) and UPF
address:
name:Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation (CRG) and UPF, Barcelona, Spain
type:PostalAddress
type:Organization
name:Universitat Pompeu Fabra (UPF)
address:
name:Universitat Pompeu Fabra (UPF), Barcelona, Spain
type:PostalAddress
type:Organization
name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP)
address:
name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP), Barcelona, Spain
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Molecular and Cellular Neurobiotechnology Group, Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain
name:Department of Cell Biology, University of Barcelona (UB), Barcelona, Spain
name:Network Biomedical Research Center for Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
name:Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation (CRG) and UPF, Barcelona, Spain
name:Universitat Pompeu Fabra (UPF), Barcelona, Spain
name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP), Barcelona, Spain
name:Institut de Medicina Predictiva i Personalitzada del CĂ ncer, Badalona, Spain
name:Molecular and Cellular Neurobiotechnology Group, Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain
name:Department of Cell Biology, University of Barcelona (UB), Barcelona, Spain
name:Network Biomedical Research Center for Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
name:Network Biomedical Research Center for Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
name:Institut Neuropatologia, Servei Anatomia PatolĂČgica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain
name:Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation (CRG) and UPF, Barcelona, Spain
name:Universitat Pompeu Fabra (UPF), Barcelona, Spain
name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP), Barcelona, Spain
name:Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation (CRG) and UPF, Barcelona, Spain
name:Universitat Pompeu Fabra (UPF), Barcelona, Spain
name:Centro de InvestigaciĂłn BiomĂ©dica en Red de EpidemiologĂa y Salud PĂșblica, (CIBERESP), Barcelona, Spain
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