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Article

Three-dimensional genome organization via triplex-forming RNAs

Publicated to:Nature Structural & Molecular Biology. 28 (11): 945-954 - 2021-11-01 28(11), DOI: 10.1038/s41594-021-00678-3

Authors: Farabella, Irene; Di Stefano, Marco; Soler-Vila, Paula; Marti-Marimon, Maria; Marti-Renom, Marc A

Affiliations

Barcelona Inst Sci & Technol, Ctr Genom Regulat, CNAG CRG, Barcelona, Spain - Author
Ctr Genom Regulat, Gene Regulat Stem Cells & Canc Program, Barcelona, Spain - Author
ICREA, Barcelona, Spain - Author
Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain - Author
Univ Montpellier, CNRS, Inst Human Genet, Montpellier, France - Author
Univ Pompeu Fabra, Barcelona, Spain - Author
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Abstract

An increasing number of long noncoding RNAs (lncRNAs) have been proposed to act as nuclear organization factors during interphase. Direct RNA-DNA interactions can be achieved by the formation of triplex helix structures where a single-stranded RNA molecule hybridizes by complementarity into the major groove of double-stranded DNA. However, whether and how these direct RNA-DNA associations influence genome structure in interphase chromosomes remain poorly understood. Here we theorize that RNA organizes the genome in space via a triplex-forming mechanism. To test this theory, we apply a computational modeling approach of chromosomes that combines restraint-based modeling with polymer physics. Our models suggest that colocalization of triplex hotspots targeted by lncRNAs could contribute to large-scale chromosome compartmentalization cooperating, rather than competing, with architectural transcription factors such as CTCF. Here the authors computationally test the hypothesis that RNA organizes the three-dimensional genome via a triplex-forming mechanism, providing evidence that lncRNA-targeted triplex hotspots can contribute to large-scale chromosome compartmentalization.

Keywords
dnahistone modificationhuman-chromosomesin-situphase-separationrevealsspatial-organizationtranscription factorstransposable elementsLong noncoding rna

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Structural & Molecular Biology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 2/72, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biophysics. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 5.04, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-07, the following number of citations:

  • WoS: 15
  • Scopus: 17
  • Europe PMC: 8
  • OpenCitations: 20
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 64.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 64 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 52.3.
  • The number of mentions on the social network X (formerly Twitter): 96 (Altmetric).
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: France.