Institut for Biomedicin

Rasmus Bak

Potent microRNA suppression by RNA Pol II-transcribed 'Tough Decoy' inhibitors

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Potent microRNA suppression by RNA Pol II-transcribed 'Tough Decoy' inhibitors. / Bak, Rasmus Otkjær; Hollensen, Anne Kruse; Primo, Maria Nascimento; Sørensen, Camilla Darum; Mikkelsen, Jacob Giehm.

I: RNA, Bind 19, Nr. 2, 2013, s. 280-293.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{4b4d3e4521c246eb831d6e2005fcc497,
title = "Potent microRNA suppression by RNA Pol II-transcribed 'Tough Decoy' inhibitors",
abstract = "MicroRNAs (miRNAs) are key regulators of gene expression and modulators of diverse biological pathways. Analyses of miRNA function as well as therapeutic managing of miRNAs rely on cellular administration of miRNA inhibitors which may be achieved by the use of viral vehicles. This study explores the miRNA-suppressive capacity of inhibitors expressed intracellularly from lentivirus-derived gene vectors. Superior activity of two decoy-type inhibitors, a {"}Bulged Sponge{"} with eight miRNA recognition sites and a hairpin-shaped {"}Tough Decoy{"} containing two miRNA recognition sites, is demonstrated in a side-by-side comparison of seven types of miRNA inhibitors transcribed as short RNAs from an RNA Pol III promoter. We find that lentiviral vectors expressing Tough Decoy inhibitors are less vulnerable than Bulged Sponge-encoding vectors to targeting by the cognate miRNA and less prone, therefore, to reductions in transfer efficiency. Importantly, it is demonstrated that Tough Decoy inhibitors retain their miRNA suppression capacity in the context of longer RNA transcripts expressed from an RNA Pol II promoter. Such RNA Pol II-transcribed Tough Decoy inhibitors are new tools in managing of miRNAs and may have potential for temporal and spatial regulation of miRNA activity as well as for therapeutic targeting of miRNAs that are aberrantly expressed in human disease.",
author = "Bak, {Rasmus Otkj{\ae}r} and Hollensen, {Anne Kruse} and Primo, {Maria Nascimento} and S{\o}rensen, {Camilla Darum} and Mikkelsen, {Jacob Giehm}",
year = "2013",
doi = "10.1261/rna.034850.112",
language = "English",
volume = "19",
pages = "280--293",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",

}

RIS

TY - JOUR

T1 - Potent microRNA suppression by RNA Pol II-transcribed 'Tough Decoy' inhibitors

AU - Bak, Rasmus Otkjær

AU - Hollensen, Anne Kruse

AU - Primo, Maria Nascimento

AU - Sørensen, Camilla Darum

AU - Mikkelsen, Jacob Giehm

PY - 2013

Y1 - 2013

N2 - MicroRNAs (miRNAs) are key regulators of gene expression and modulators of diverse biological pathways. Analyses of miRNA function as well as therapeutic managing of miRNAs rely on cellular administration of miRNA inhibitors which may be achieved by the use of viral vehicles. This study explores the miRNA-suppressive capacity of inhibitors expressed intracellularly from lentivirus-derived gene vectors. Superior activity of two decoy-type inhibitors, a "Bulged Sponge" with eight miRNA recognition sites and a hairpin-shaped "Tough Decoy" containing two miRNA recognition sites, is demonstrated in a side-by-side comparison of seven types of miRNA inhibitors transcribed as short RNAs from an RNA Pol III promoter. We find that lentiviral vectors expressing Tough Decoy inhibitors are less vulnerable than Bulged Sponge-encoding vectors to targeting by the cognate miRNA and less prone, therefore, to reductions in transfer efficiency. Importantly, it is demonstrated that Tough Decoy inhibitors retain their miRNA suppression capacity in the context of longer RNA transcripts expressed from an RNA Pol II promoter. Such RNA Pol II-transcribed Tough Decoy inhibitors are new tools in managing of miRNAs and may have potential for temporal and spatial regulation of miRNA activity as well as for therapeutic targeting of miRNAs that are aberrantly expressed in human disease.

AB - MicroRNAs (miRNAs) are key regulators of gene expression and modulators of diverse biological pathways. Analyses of miRNA function as well as therapeutic managing of miRNAs rely on cellular administration of miRNA inhibitors which may be achieved by the use of viral vehicles. This study explores the miRNA-suppressive capacity of inhibitors expressed intracellularly from lentivirus-derived gene vectors. Superior activity of two decoy-type inhibitors, a "Bulged Sponge" with eight miRNA recognition sites and a hairpin-shaped "Tough Decoy" containing two miRNA recognition sites, is demonstrated in a side-by-side comparison of seven types of miRNA inhibitors transcribed as short RNAs from an RNA Pol III promoter. We find that lentiviral vectors expressing Tough Decoy inhibitors are less vulnerable than Bulged Sponge-encoding vectors to targeting by the cognate miRNA and less prone, therefore, to reductions in transfer efficiency. Importantly, it is demonstrated that Tough Decoy inhibitors retain their miRNA suppression capacity in the context of longer RNA transcripts expressed from an RNA Pol II promoter. Such RNA Pol II-transcribed Tough Decoy inhibitors are new tools in managing of miRNAs and may have potential for temporal and spatial regulation of miRNA activity as well as for therapeutic targeting of miRNAs that are aberrantly expressed in human disease.

U2 - 10.1261/rna.034850.112

DO - 10.1261/rna.034850.112

M3 - Journal article

C2 - 23249752

VL - 19

SP - 280

EP - 293

JO - RNA

JF - RNA

SN - 1355-8382

IS - 2

ER -