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Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6

DNA replication occurs on mammalian chromosomes in a cell-type distinctive temporal order known as the replication timing program. We previously found that disruption of the noncanonical lncRNA genes ASAR6 and ASAR15 results in delayed replication timing and delayed mitotic chromosome condensation o...

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Autores principales: Heskett, Michael B., Smith, Leslie G., Spellman, Paul, Thayer, Mathew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266157/
https://www.ncbi.nlm.nih.gov/pubmed/32144193
http://dx.doi.org/10.1261/rna.073114.119
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author Heskett, Michael B.
Smith, Leslie G.
Spellman, Paul
Thayer, Mathew J.
author_facet Heskett, Michael B.
Smith, Leslie G.
Spellman, Paul
Thayer, Mathew J.
author_sort Heskett, Michael B.
collection PubMed
description DNA replication occurs on mammalian chromosomes in a cell-type distinctive temporal order known as the replication timing program. We previously found that disruption of the noncanonical lncRNA genes ASAR6 and ASAR15 results in delayed replication timing and delayed mitotic chromosome condensation of human chromosomes 6 and 15, respectively. ASAR6 and ASAR15 display random monoallelic expression and display asynchronous replication between alleles that is coordinated with other random monoallelic genes on their respective chromosomes. Disruption of the expressed allele, but not the silent allele, of ASAR6 leads to delayed replication, activation of the previously silent alleles of linked monoallelic genes, and structural instability of human chromosome 6. In this report, we describe a second lncRNA gene (ASAR6-141) on human chromosome 6 that when disrupted results in delayed replication timing in cis. ASAR6-141 is subject to random monoallelic expression and asynchronous replication and is expressed from the opposite chromosome 6 homolog as ASAR6. ASAR6-141 RNA, like ASAR6 and ASAR15 RNAs, contains a high L1 content and remains associated with the chromosome territory where it is transcribed. Three classes of cis-acting elements control proper chromosome function in mammals: origins of replication, centromeres, and telomeres, which are responsible for replication, segregation, and stability of all chromosomes. Our work supports a fourth type of essential chromosomal element, the “Inactivation/Stability Center,” which expresses ASAR lncRNAs responsible for proper replication timing, monoallelic expression, and structural stability of each chromosome.
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spelling pubmed-72661572020-06-12 Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6 Heskett, Michael B. Smith, Leslie G. Spellman, Paul Thayer, Mathew J. RNA Article DNA replication occurs on mammalian chromosomes in a cell-type distinctive temporal order known as the replication timing program. We previously found that disruption of the noncanonical lncRNA genes ASAR6 and ASAR15 results in delayed replication timing and delayed mitotic chromosome condensation of human chromosomes 6 and 15, respectively. ASAR6 and ASAR15 display random monoallelic expression and display asynchronous replication between alleles that is coordinated with other random monoallelic genes on their respective chromosomes. Disruption of the expressed allele, but not the silent allele, of ASAR6 leads to delayed replication, activation of the previously silent alleles of linked monoallelic genes, and structural instability of human chromosome 6. In this report, we describe a second lncRNA gene (ASAR6-141) on human chromosome 6 that when disrupted results in delayed replication timing in cis. ASAR6-141 is subject to random monoallelic expression and asynchronous replication and is expressed from the opposite chromosome 6 homolog as ASAR6. ASAR6-141 RNA, like ASAR6 and ASAR15 RNAs, contains a high L1 content and remains associated with the chromosome territory where it is transcribed. Three classes of cis-acting elements control proper chromosome function in mammals: origins of replication, centromeres, and telomeres, which are responsible for replication, segregation, and stability of all chromosomes. Our work supports a fourth type of essential chromosomal element, the “Inactivation/Stability Center,” which expresses ASAR lncRNAs responsible for proper replication timing, monoallelic expression, and structural stability of each chromosome. Cold Spring Harbor Laboratory Press 2020-06 /pmc/articles/PMC7266157/ /pubmed/32144193 http://dx.doi.org/10.1261/rna.073114.119 Text en © 2020 Heskett et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Heskett, Michael B.
Smith, Leslie G.
Spellman, Paul
Thayer, Mathew J.
Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6
title Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6
title_full Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6
title_fullStr Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6
title_full_unstemmed Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6
title_short Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6
title_sort reciprocal monoallelic expression of asar lncrna genes controls replication timing of human chromosome 6
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266157/
https://www.ncbi.nlm.nih.gov/pubmed/32144193
http://dx.doi.org/10.1261/rna.073114.119
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