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Transcriptional kinetics and molecular functions of long noncoding RNAs

An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared...

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Autores principales: Johnsson, Per, Ziegenhain, Christoph, Hartmanis, Leonard, Hendriks, Gert-Jan, Hagemann-Jensen, Michael, Reinius, Björn, Sandberg, Rickard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920890/
https://www.ncbi.nlm.nih.gov/pubmed/35241826
http://dx.doi.org/10.1038/s41588-022-01014-1
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author Johnsson, Per
Ziegenhain, Christoph
Hartmanis, Leonard
Hendriks, Gert-Jan
Hagemann-Jensen, Michael
Reinius, Björn
Sandberg, Rickard
author_facet Johnsson, Per
Ziegenhain, Christoph
Hartmanis, Leonard
Hendriks, Gert-Jan
Hagemann-Jensen, Michael
Reinius, Björn
Sandberg, Rickard
author_sort Johnsson, Per
collection PubMed
description An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared to messenger RNAs, lncRNAs have twice as long duration between two transcriptional bursts. Additionally, we observed increased cell-to-cell variability in lncRNA expression due to lower frequency bursting producing larger numbers of RNA molecules. Exploiting heterogeneity in asynchronously growing cells, we identified and experimentally validated lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis. Finally, we identified cis-functioning lncRNAs and showed that knockdown of these lncRNAs modulated the nearby protein-coding gene’s transcriptional burst frequency or size. In summary, we identified distinct transcriptional regulation of lncRNAs and demonstrated a role for lncRNAs in the regulation of mRNA transcriptional bursting.
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spelling pubmed-89208902022-03-30 Transcriptional kinetics and molecular functions of long noncoding RNAs Johnsson, Per Ziegenhain, Christoph Hartmanis, Leonard Hendriks, Gert-Jan Hagemann-Jensen, Michael Reinius, Björn Sandberg, Rickard Nat Genet Article An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared to messenger RNAs, lncRNAs have twice as long duration between two transcriptional bursts. Additionally, we observed increased cell-to-cell variability in lncRNA expression due to lower frequency bursting producing larger numbers of RNA molecules. Exploiting heterogeneity in asynchronously growing cells, we identified and experimentally validated lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis. Finally, we identified cis-functioning lncRNAs and showed that knockdown of these lncRNAs modulated the nearby protein-coding gene’s transcriptional burst frequency or size. In summary, we identified distinct transcriptional regulation of lncRNAs and demonstrated a role for lncRNAs in the regulation of mRNA transcriptional bursting. Nature Publishing Group US 2022-03-03 2022 /pmc/articles/PMC8920890/ /pubmed/35241826 http://dx.doi.org/10.1038/s41588-022-01014-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Johnsson, Per
Ziegenhain, Christoph
Hartmanis, Leonard
Hendriks, Gert-Jan
Hagemann-Jensen, Michael
Reinius, Björn
Sandberg, Rickard
Transcriptional kinetics and molecular functions of long noncoding RNAs
title Transcriptional kinetics and molecular functions of long noncoding RNAs
title_full Transcriptional kinetics and molecular functions of long noncoding RNAs
title_fullStr Transcriptional kinetics and molecular functions of long noncoding RNAs
title_full_unstemmed Transcriptional kinetics and molecular functions of long noncoding RNAs
title_short Transcriptional kinetics and molecular functions of long noncoding RNAs
title_sort transcriptional kinetics and molecular functions of long noncoding rnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920890/
https://www.ncbi.nlm.nih.gov/pubmed/35241826
http://dx.doi.org/10.1038/s41588-022-01014-1
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