Individual long non-coding RNAs have no overt functions in zebrafish embryogenesis, viability and fertility

Abstract
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Abstract

Hundreds of long non-coding RNAs (lncRNAs) have been identified as potential regulators of gene expression, but their functions remain largely unknown. To study the role of lncRNAs during vertebrate development, we selected 25 zebrafish lncRNAs based on their conservation, expression profile or proximity to developmental regulators, and used CRISPR-Cas9 to generate 32 deletion alleles. We observed altered transcription of neighboring genes in some mutants, but none of the lncRNAs were required for embryogenesis, viability or fertility. Even RNAs with previously proposed non-coding functions (cyrano and squint) and other conserved lncRNAs (gas5 and lnc-setd1ba) were dispensable. In one case (lnc-phox2bb), absence of putative DNA regulatory-elements, but not of the lncRNA transcript itself, resulted in abnormal development. LncRNAs might have redundant, subtle, or context-dependent roles, but extrapolation from our results suggests that the majority of individual zebrafish lncRNAs have no overt roles in embryogenesis, viability and fertility.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.Previously published datasets used in this manuscript:SRP013950, GSE32880, GSE37453, GSE32898, GSE46512

The following previously published data sets were used

1. Haberle V et al
(2014) Two independent transcription initiation codes overlap on vertebrate core promoters.
NCBI Bioproject, SRP013950.

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA169500
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(2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution.
NCBI Gene Expression Omnibus, GSE32880.

https://www.ncbi.nlm.nih.gov/bioproject/?term=GSE32880
1. Ulitsky I et al
(2012) Extensive alternative polyadenylation during zebrafish development.
NCBI Gene Expression Omnibus, GSE37453.

https://www.ncbi.nlm.nih.gov/bioproject/?term=GSE37453
1. Pauli A et al
(2012) Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis.
NCBI Gene Expression Omnibus, GSE32898.

https://www.ncbi.nlm.nih.gov/bioproject/?term=GSE32898
1. Guo-Liang Chew
(2013) Ribosome profiling reveals resemblance between long non-coding RNAs and 5' leaders of coding RNAs.
NCBI Gene Expression Omnibus, GSE46512.

https://www.ncbi.nlm.nih.gov/bioproject/?term=GSE46512

Article and author information

Author details

Mehdi Goudarzi

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

For correspondence
mgoudarzi@fas.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6669-5800
Kathryn Berg

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Lindsey M Pieper

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Alexander F Schier

Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

For correspondence
schier@fas.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7645-5325

Funding

NIH Office of the Director (R01HD076708)

Alexander F Schier

Leopoldina (Postdoctorial fellowship LPDS2014-01)

Mehdi Goudarzi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.