From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond
Open accessAbstract
Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.
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DDR activation depends on noncoding RNAs such as dilncRNA and DDRNA generated at exposed DNA ends, including dysfunctional telomeres.
“The discovery that DDR activation depends on noncoding RNAs, such as damage-induced long non-coding RNAs (dilncRNA) and DNA damage-response RNAs (DDRNA), generated at exposed DNA ends, including dysfunctional telomeres, make such RNAs attractive targets for potential therapeutic interventions196.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [196]
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Telomere dysfunction in ageing and age-related diseases
Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00842-x · Cited by 754 · see citing works
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Self-citationAguado, J., Sola-Carvajal, A., Cancila, V., Revêchon, G., Ong, P. F., Jones-Weinert, C. W., Wallén Arzt, E., Lattanzi, G., Dreesen, O., Tripodo, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13018-3 · Cited by 133 · see citing works
Self-citation
- Authors
- Michelini, F., Jalihal, A. P., Francia, S., Meers, C., Neeb, Z. T., Rossiello, F., Gioia, U., Aguado, J., Jones-Weinert, C., Luke, B., Biamonti, G., Nowacki, M., Storici, F., Carninci, P., Walter, N. G., & d’Adda di Fagagna, F.
- Affiliations
- IFOM (IT)
- University of Michigan (US)
- Georgia Institute of Technology (US)
- University of Bern (CH)
- Johannes Gutenberg University Mainz (DE)
- Istituto di Genetica Molecolare (IT)
- RIKEN (JP)
- IFOM − The FIRC Institute of Molecular Oncology, Milan, 20139, Italy
- Corresponding author
- Michelini, Flavia
- ORCID
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-03-30
- Volume
- 118
- Issue
- 8
- Pages
- 4365-4403
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- PMC
- PMC7717669
- OpenAlex
- W2794746967
- Cited by
- 85
- References
- 418
- Citations by year
- 2026: 10 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 12 · 2021: 13 · 2020: 13 · 2019: 13 · 2018: 4
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Chemical Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- Howard Hughes Medical Institute (55108574)
- Collegio Ghislieri di Pavia
- Division of Molecular and Cellular Biosciences (MCB-1615335)
- Schweizerischer Nationalfonds zur F?rderung der Wissenschaftlichen Forschung (31003A_146257, 31003A_166407)
- Associazione Italiana per la Ricerca sul Cancro (15273)
- Fondazione Cariplo (2014-1215)
- U.S. Department of Education (P200A150130-16)
- Comprehensive Cancer Center, University of Michigan
- FP7 Ideas: European Research Council (260358)
- National Institute of General Medical Sciences (GM115927, GM122803, GM118524, GM062357)
- H2020 European Research Council (681178)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- RNA, genome stability, non-coding RNA, DNA damage signaling, DNA repair, telomere maintenance, genome rearrangement, single-molecule RNA detection, RNA therapeutics
- MeSH terms
- DNA Damage, Gene Expression Regulation, Humans, Transcription, Genetic, RNA-Binding Proteins, RNA, Untranslated, RNA Interference, Genomic Instability, DNA Breaks, Double-Stranded
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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