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Article

Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs

by 1,2 and 1,2,*
1
Research Center of Biotechnology, Institute of Bioengineering, Russian Academy of Science, 119071 Moscow, Russia
2
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, 141701 Moscow Region, Russia
*
Author to whom correspondence should be addressed.
Genes 2020, 11(12), 1483; https://doi.org/10.3390/genes11121483
Received: 24 October 2020 / Revised: 3 December 2020 / Accepted: 4 December 2020 / Published: 10 December 2020
(This article belongs to the Special Issue Algorithms and Workflows in RNA Bioinformatics)
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. View Full-Text
Keywords: long non-coding RNAs; RNA-RNA interactions; nascent transcripts; gene regulation long non-coding RNAs; RNA-RNA interactions; nascent transcripts; gene regulation
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MDPI and ACS Style

Antonov, I.; Medvedeva, Y. Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs. Genes 2020, 11, 1483. https://doi.org/10.3390/genes11121483

AMA Style

Antonov I, Medvedeva Y. Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs. Genes. 2020; 11(12):1483. https://doi.org/10.3390/genes11121483

Chicago/Turabian Style

Antonov, Ivan, and Yulia Medvedeva. 2020. "Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs" Genes 11, no. 12: 1483. https://doi.org/10.3390/genes11121483

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