Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution

Thousands of long intervening noncoding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data to identify more than 550 distinct lincRNAs in zebrafish. Although these s...

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Main Authors: Ulitsky, Igor, Shkumatava, Alena, Jan, Calvin H., Sive, Hazel L., Bartel, David
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier B.V. 2014
Online Access:http://hdl.handle.net/1721.1/84684
https://orcid.org/0000-0002-3872-2856
https://orcid.org/0000-0002-4890-424X
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author Ulitsky, Igor
Shkumatava, Alena
Jan, Calvin H.
Sive, Hazel L.
Bartel, David
Jan, Calvin H.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Ulitsky, Igor
Shkumatava, Alena
Jan, Calvin H.
Sive, Hazel L.
Bartel, David
Jan, Calvin H.
author_sort Ulitsky, Igor
collection MIT
description Thousands of long intervening noncoding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation.
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spelling mit-1721.1/846842022-09-28T17:48:24Z Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution Ulitsky, Igor Shkumatava, Alena Jan, Calvin H. Sive, Hazel L. Bartel, David Jan, Calvin H. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ulitsky, Igor Shkumatava, Alena Jan, Calvin H. Sive, Hazel L. Bartel, David Thousands of long intervening noncoding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation. National Institutes of Health (U.S.) (grant GM067031) European Molecular Biology Organization (long-term fellowship) National Science Foundation (U.S.) (Predoctoral fellowship) Human Frontier Science Program (Strasbourg, France) (Long-term Fellowship) 2014-02-07T17:54:02Z 2014-02-07T17:54:02Z 2011-12 Article http://purl.org/eprint/type/JournalArticle 00928674 http://hdl.handle.net/1721.1/84684 Ulitsky, Igor, Alena Shkumatava, Calvin H. Jan, Hazel Sive, and David P. Bartel. “Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution.” Cell 147, no. 7 (December 2011): 1537-1550. © 2011 Elsevier Inc. https://orcid.org/0000-0002-3872-2856 https://orcid.org/0000-0002-4890-424X en_US http://dx.doi.org/10.1016/j.cell.2011.11.055 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier Open Archive
spellingShingle Ulitsky, Igor
Shkumatava, Alena
Jan, Calvin H.
Sive, Hazel L.
Bartel, David
Jan, Calvin H.
Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
title Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
title_full Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
title_fullStr Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
title_full_unstemmed Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
title_short Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
title_sort conserved function of lincrnas in vertebrate embryonic development despite rapid sequence evolution
url http://hdl.handle.net/1721.1/84684
https://orcid.org/0000-0002-3872-2856
https://orcid.org/0000-0002-4890-424X
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