A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs

Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo....

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Main Authors: Fulga, Tudor A., McNeill, Elizabeth M., Binari, Richard, Yelick, Julia, Blanche, Alexandra, Booker, Matthew, Steinkraus, Bruno R., Schnall-Levin, Michael, Zhao, Yong, DeLuca, Todd, Bejarano, Fernando, Han, Zhe, Lai, Eric C., Wall, Dennis P., Perrimon, Norbert, Van Vactor, David
Format: Online
Language:English
Published: Nature Pub. Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471878/
id pubmed-4471878
recordtype oai_dc
spelling pubmed-44718782015-09-11 A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs Fulga, Tudor A. McNeill, Elizabeth M. Binari, Richard Yelick, Julia Blanche, Alexandra Booker, Matthew Steinkraus, Bruno R. Schnall-Levin, Michael Zhao, Yong DeLuca, Todd Bejarano, Fernando Han, Zhe Lai, Eric C. Wall, Dennis P. Perrimon, Norbert Van Vactor, David Article Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo. However, the application of these loss-of-function strategies has been limited. Here we offer a comprehensive library of 141 conditional miRNA sponges targeting well-conserved miRNAs in Drosophila. Ubiquitous miRNA sponge delivery and consequent systemic miRNA inhibition uncovers a relatively small number of miRNA families underlying viability and gross morphogenesis, with false discovery rates in the 4–8% range. In contrast, tissue-specific silencing of muscle-enriched miRNAs reveals a surprisingly large number of novel miRNA contributions to the maintenance of adult indirect flight muscle structure and function. A strong correlation between miRNA abundance and physiological relevance is not observed, underscoring the importance of unbiased screens when assessing the contributions of miRNAs to complex biological processes. Nature Pub. Group 2015-06-17 /pmc/articles/PMC4471878/ /pubmed/26081261 http://dx.doi.org/10.1038/ncomms8279 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fulga, Tudor A.
McNeill, Elizabeth M.
Binari, Richard
Yelick, Julia
Blanche, Alexandra
Booker, Matthew
Steinkraus, Bruno R.
Schnall-Levin, Michael
Zhao, Yong
DeLuca, Todd
Bejarano, Fernando
Han, Zhe
Lai, Eric C.
Wall, Dennis P.
Perrimon, Norbert
Van Vactor, David
spellingShingle Fulga, Tudor A.
McNeill, Elizabeth M.
Binari, Richard
Yelick, Julia
Blanche, Alexandra
Booker, Matthew
Steinkraus, Bruno R.
Schnall-Levin, Michael
Zhao, Yong
DeLuca, Todd
Bejarano, Fernando
Han, Zhe
Lai, Eric C.
Wall, Dennis P.
Perrimon, Norbert
Van Vactor, David
A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs
author_facet Fulga, Tudor A.
McNeill, Elizabeth M.
Binari, Richard
Yelick, Julia
Blanche, Alexandra
Booker, Matthew
Steinkraus, Bruno R.
Schnall-Levin, Michael
Zhao, Yong
DeLuca, Todd
Bejarano, Fernando
Han, Zhe
Lai, Eric C.
Wall, Dennis P.
Perrimon, Norbert
Van Vactor, David
author_sort Fulga, Tudor A.
title A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs
title_short A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs
title_full A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs
title_fullStr A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs
title_full_unstemmed A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs
title_sort transgenic resource for conditional competitive inhibition of conserved drosophila micrornas
description Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo. However, the application of these loss-of-function strategies has been limited. Here we offer a comprehensive library of 141 conditional miRNA sponges targeting well-conserved miRNAs in Drosophila. Ubiquitous miRNA sponge delivery and consequent systemic miRNA inhibition uncovers a relatively small number of miRNA families underlying viability and gross morphogenesis, with false discovery rates in the 4–8% range. In contrast, tissue-specific silencing of muscle-enriched miRNAs reveals a surprisingly large number of novel miRNA contributions to the maintenance of adult indirect flight muscle structure and function. A strong correlation between miRNA abundance and physiological relevance is not observed, underscoring the importance of unbiased screens when assessing the contributions of miRNAs to complex biological processes.
publisher Nature Pub. Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471878/
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