How RNA impacts DNA repair

Tsao, Ning; Ashour, Mohamed E.; Mosammaparast, Nima

doi:10.1016/j.dnarep.2023.103564

Cited by 4 publications

(2 citation statements)

References 72 publications

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“…An increasing body of work in the last two decades has shown that RNAs play an important role in various DNA repair processes 3,4 . Previous studies have revealed a role for the activating signal cointegrator complex (ASCC) in base damage repair, particularly in response to alkylation and UV damage [5][6][7][8] .…”

Section: Main Sectionmentioning

confidence: 99%

YTHDC1 cooperates with the THO complex to prevent RNA damage-induced DNA breaks

Tsao,

Olabode,

Rodell

et al. 2024

Preprint

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SummaryCertain environmental toxins are nucleic acid damaging agents, as are many chemotherapeutics used for cancer therapy. These agents induce various adducts in DNA as well as RNA. Indeed, most of the nucleic acid adducts (>90%) formed due to these chemicals, such as alkylating agents, occur in RNA1. However, compared to the well-studied mechanisms for DNA alkylation repair, the biological consequences of RNA damage are largely unexplored. Here, we demonstrate that RNA damage can directly result in loss of genome integrity. Specifically, we show that a human YTH domain-containing protein, YTHDC1, regulates alkylation damage responses in association with the THO complex (THOC)2. In addition to its established binding toN6-methyladenosine (m6A)-containing RNAs, YTHDC1 binds toN1-methyladenosine (m1A)-containing RNAs upon alkylation. In the absence of YTHDC1, alkylation damage results in increased alkylation damage sensitivity and DNA breaks. Such phenotypes are fully attributable to RNA damage, since an RNA-specific dealkylase can rescue these phenotypes. TheseRNAdamage-induced DNAbreaks (RDIBs) depend on R-loop formation, which in turn are processed by factors involved in transcription-coupled nucleotide excision repair. Strikingly, in the absence of YTHDC1 or THOC, an RNA m1A methyltransferase targeted to the nucleus is sufficient to induce DNA breaks. Our results uncover a unique role for YTHDC1-THOC in base damage responses by preventing RDIBs, providing definitive evidence for how damaged RNAs can impact genomic integrity.

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Section: Main Sectionmentioning

confidence: 99%

YTHDC1 cooperates with the THO complex to prevent RNA damage-induced DNA breaks

Tsao,

Olabode,

Rodell

et al. 2024

Preprint

Self Cite

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“…Another example is the process of reverse transcription in retroviruses, where viral RNA is reverse transcribed into DNA. For instance, in RNA interference (RNAi), small RNA molecules can bind to complementary sequences in mRNA molecules, leading to their degradation and thus preventing their translation into proteins [ 47 ]. Another example is the clustered regularly interspaced short palindromic repeats system, a bacterial defense mechanism that has been adapted for genome editing.…”

Section: Types Of Interactionsmentioning

confidence: 99%

A Hitchhiker's guide to RNA–RNA structure and interaction prediction tools

Tieng,

Abdullah-Zawawi,

Md Shahri

et al. 2023

Briefings in Bioinformatics

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RNA biology has risen to prominence after a remarkable discovery of diverse functions of noncoding RNA (ncRNA). Most untranslated transcripts often exert their regulatory functions into RNA–RNA complexes via base pairing with complementary sequences in other RNAs. An interplay between RNAs is essential, as it possesses various functional roles in human cells, including genetic translation, RNA splicing, editing, ribosomal RNA maturation, RNA degradation and the regulation of metabolic pathways/riboswitches. Moreover, the pervasive transcription of the human genome allows for the discovery of novel genomic functions via RNA interactome investigation. The advancement of experimental procedures has resulted in an explosion of documented data, necessitating the development of efficient and precise computational tools and algorithms. This review provides an extensive update on RNA–RNA interaction (RRI) analysis via thermodynamic- and comparative-based RNA secondary structure prediction (RSP) and RNA–RNA interaction prediction (RIP) tools and their general functions. We also highlighted the current knowledge of RRIs and the limitations of RNA interactome mapping via experimental data. Then, the gap between RSP and RIP, the importance of RNA homologues, the relationship between pseudoknots, and RNA folding thermodynamics are discussed. It is hoped that these emerging prediction tools will deepen the understanding of RNA-associated interactions in human diseases and hasten treatment processes.

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The role of rRNA in maintaining genome stability

Li,

2024

DNA Repair

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How RNA impacts DNA repair

Cited by 4 publications

References 72 publications

YTHDC1 cooperates with the THO complex to prevent RNA damage-induced DNA breaks

YTHDC1 cooperates with the THO complex to prevent RNA damage-induced DNA breaks

A Hitchhiker's guide to RNA–RNA structure and interaction prediction tools

The role of rRNA in maintaining genome stability

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