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Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation

Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses unc...

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Autores principales: Warnefors, Maria, Mössinger, Katharina, Halbert, Jean, Studer, Tania, VandeBerg, John L., Lindgren, Isa, Fallahshahroudi, Amir, Jensen, Per, Kaessmann, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741053/
https://www.ncbi.nlm.nih.gov/pubmed/29079676
http://dx.doi.org/10.1101/gr.225391.117
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author Warnefors, Maria
Mössinger, Katharina
Halbert, Jean
Studer, Tania
VandeBerg, John L.
Lindgren, Isa
Fallahshahroudi, Amir
Jensen, Per
Kaessmann, Henrik
author_facet Warnefors, Maria
Mössinger, Katharina
Halbert, Jean
Studer, Tania
VandeBerg, John L.
Lindgren, Isa
Fallahshahroudi, Amir
Jensen, Per
Kaessmann, Henrik
author_sort Warnefors, Maria
collection PubMed
description Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z Chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W Chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z Chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalize male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism.
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spelling pubmed-57410532018-01-23 Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation Warnefors, Maria Mössinger, Katharina Halbert, Jean Studer, Tania VandeBerg, John L. Lindgren, Isa Fallahshahroudi, Amir Jensen, Per Kaessmann, Henrik Genome Res Research Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z Chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W Chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z Chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalize male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism. Cold Spring Harbor Laboratory Press 2017-12 /pmc/articles/PMC5741053/ /pubmed/29079676 http://dx.doi.org/10.1101/gr.225391.117 Text en © 2017 Warnefors et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Warnefors, Maria
Mössinger, Katharina
Halbert, Jean
Studer, Tania
VandeBerg, John L.
Lindgren, Isa
Fallahshahroudi, Amir
Jensen, Per
Kaessmann, Henrik
Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
title Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
title_full Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
title_fullStr Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
title_full_unstemmed Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
title_short Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
title_sort sex-biased microrna expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741053/
https://www.ncbi.nlm.nih.gov/pubmed/29079676
http://dx.doi.org/10.1101/gr.225391.117
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