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Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs
Although thousands of mammalian long non-coding RNAs (lncRNAs) have been reported in the last decade, their functional annotation remains limited. A wet-lab approach to detect functions of a novel lncRNA usually includes its knockdown followed by RNA sequencing and identification of the deferentiall...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764144/ https://www.ncbi.nlm.nih.gov/pubmed/33321875 http://dx.doi.org/10.3390/genes11121483 |
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author | Antonov, Ivan Medvedeva, Yulia |
author_facet | Antonov, Ivan Medvedeva, Yulia |
author_sort | Antonov, Ivan |
collection | PubMed |
description | Although thousands of mammalian long non-coding RNAs (lncRNAs) have been reported in the last decade, their functional annotation remains limited. A wet-lab approach to detect functions of a novel lncRNA usually includes its knockdown followed by RNA sequencing and identification of the deferentially expressed genes. However, identification of the molecular mechanism(s) used by the lncRNA to regulate its targets frequently becomes a challenge. Previously, we developed the ASSA algorithm that detects statistically significant inter-molecular RNA-RNA interactions. Here we designed a workflow that uses ASSA predictions to estimate the ability of an lncRNA to function via direct base pairing with the target transcripts (co- or post-transcriptionally). The workflow was applied to 300+ lncRNA knockdown experiments from the FANTOM6 pilot project producing statistically significant predictions for 71 unique lncRNAs (104 knockdowns). Surprisingly, the majority of these lncRNAs were likely to function co-transcriptionally, i.e., hybridize with the nascent transcripts of the target genes. Moreover, a number of the obtained predictions were supported by independent iMARGI experimental data on co-localization of lncRNA and chromatin. We detected an evolutionarily conserved lncRNA CHASERR (AC013394.2 or LINC01578) that could regulate target genes co-transcriptionally via interaction with a nascent transcript by directing CHD2 helicase. The obtained results suggested that this nuclear lncRNA may be able to activate expression of the target genes in trans by base-pairing with the nascent transcripts and directing the CHD2 helicase to the regulated promoters leading to open the chromatin and active transcription. Our study highlights the possible importance of base-pairing between nuclear lncRNAs and nascent transcripts for the regulation of gene expression. |
format | Online Article Text |
id | pubmed-7764144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77641442020-12-27 Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs Antonov, Ivan Medvedeva, Yulia Genes (Basel) Article Although thousands of mammalian long non-coding RNAs (lncRNAs) have been reported in the last decade, their functional annotation remains limited. A wet-lab approach to detect functions of a novel lncRNA usually includes its knockdown followed by RNA sequencing and identification of the deferentially expressed genes. However, identification of the molecular mechanism(s) used by the lncRNA to regulate its targets frequently becomes a challenge. Previously, we developed the ASSA algorithm that detects statistically significant inter-molecular RNA-RNA interactions. Here we designed a workflow that uses ASSA predictions to estimate the ability of an lncRNA to function via direct base pairing with the target transcripts (co- or post-transcriptionally). The workflow was applied to 300+ lncRNA knockdown experiments from the FANTOM6 pilot project producing statistically significant predictions for 71 unique lncRNAs (104 knockdowns). Surprisingly, the majority of these lncRNAs were likely to function co-transcriptionally, i.e., hybridize with the nascent transcripts of the target genes. Moreover, a number of the obtained predictions were supported by independent iMARGI experimental data on co-localization of lncRNA and chromatin. We detected an evolutionarily conserved lncRNA CHASERR (AC013394.2 or LINC01578) that could regulate target genes co-transcriptionally via interaction with a nascent transcript by directing CHD2 helicase. The obtained results suggested that this nuclear lncRNA may be able to activate expression of the target genes in trans by base-pairing with the nascent transcripts and directing the CHD2 helicase to the regulated promoters leading to open the chromatin and active transcription. Our study highlights the possible importance of base-pairing between nuclear lncRNAs and nascent transcripts for the regulation of gene expression. MDPI 2020-12-10 /pmc/articles/PMC7764144/ /pubmed/33321875 http://dx.doi.org/10.3390/genes11121483 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Antonov, Ivan Medvedeva, Yulia Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs |
title | Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs |
title_full | Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs |
title_fullStr | Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs |
title_full_unstemmed | Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs |
title_short | Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs |
title_sort | direct interactions with nascent transcripts is potentially a common targeting mechanism of long non-coding rnas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764144/ https://www.ncbi.nlm.nih.gov/pubmed/33321875 http://dx.doi.org/10.3390/genes11121483 |
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