Evidence map›Paper›PMID 39349456›Full record

ArticleNature communications2024

NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity.

Susan Kilgas, Aleem Syed, Patrick Toolan-Kerr, Michelle L Swift, Shrabasti Roychoudhury, Aniruddha Sarkar, Sarah Wilkins, Mikayla Quigley, Anna R Poetsch, Maria Victoria Botuyan and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Susan KilgasDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1012-9230
Aleem SyedDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7942-3900
Patrick Toolan-KerrThe Francis Crick Institute, 1 Midland Road, London, UK.
Michelle L SwiftDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3645-1308
Shrabasti RoychoudhuryDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Aniruddha SarkarDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9393-1335
Sarah WilkinsDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Mikayla QuigleyDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5143-9879
Anna R PoetschBiotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47-49, Dresden, Germany.
Maria Victoria BotuyanDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-6466-7432
Gaofeng CuiDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-5267-9033
Georges MerDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-1900-1578
Jernej UleThe Francis Crick Institute, 1 Midland Road, London, UK.
Pascal DranéDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. pdrane@hunter.bio.ORCID 0009-0002-9413-4159
Dipanjan ChowdhuryDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Dipanjan_Chowdhury@dfci.harvard.edu.ORCID 0000-0001-5645-3752

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI MALCOLM S. CAPEL · 2018 to 2026
$34.2M
Structural Biology of Lysine Methylation in DNA Damage and Checkpoint SignalingR01CA132878 · NCI · MAYO CLINIC ROCHESTER · PI Georges Mer · 2008 to 2026
$4.5M
Structural biology of DNA damage response in chromatinR35GM136262 · NIGMS · MAYO CLINIC ROCHESTER · PI MER, GEORGES · 2020 to 2025
$4.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Elucidating the molecular mechanism and physiological relevance of TIRR mediated inhibition of p53R01CA264900 · NCI · DANA-FARBER CANCER INST · PI Dipanjan Chowdhury · 2022 to 2026
$1.9M
Investigating 53BP1 'dephosphorylation' as a critical determinant of PARPR01CA208244 · NCI · DANA-FARBER CANCER INST · PI CHOWDHURY, DIPANJAN · 2017 to 2021
$1.9M
Cancer Therapeutic Resistance: Implication of AcAPE1 Mediated DNA Repair and T-Cell Based ImmunotherapyK00CA223064 · NCI · DANA-FARBER CANCER INST · PI ROYCHOUDHURY, SHRABASTI · 2019 to 2022
$392k
Evaluating the mechanism by which the DYNLL1-MRE11 complex regulates DNA end resection and genome stability.F32GM149115 · NIGMS · DANA-FARBER CANCER INST · PI SWIFT, MICHELLE · 2023 to 2024
$143k
NCI NIH HHS K00 CA223064NCI NIH HHS R01 CA132878NCI NIH HHS R01 CA208244NCI NIH HHS R01 CA264900NIGMS NIH HHS F32 GM149115NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R35 GM136262NIH HHS S10 OD021527Wellcome Trust CC0102
6 · The paper itself

Abstract

Tudor Interacting Repair Regulator (TIRR) is an RNA-binding protein (RBP) that interacts directly with 53BP1, restricting its access to DNA double-strand breaks (DSBs) and its association with p53. We utilized iCLIP to identify RNAs that directly bind to TIRR within cells, identifying the long non-coding RNA NEAT1 as the primary RNA partner. The high affinity of TIRR for NEAT1 is due to prevalent G-rich motifs in the short isoform (NEAT1_1) region of NEAT1. This interaction destabilizes the TIRR/53BP1 complex, promoting 53BP1's function. NEAT1_1 is enriched during the G1 phase of the cell cycle, thereby ensuring that TIRR-dependent inhibition of 53BP1's function is cell cycle-dependent. TDP-43, an RBP that is implicated in neurodegenerative diseases, modulates the TIRR/53BP1 complex by promoting the production of the NEAT1 short isoform, NEAT1_1. Together, we infer that NEAT1_1, and factors regulating NEAT1_1, may impact 53BP1-dependent DNA repair processes, with implications for a spectrum of diseases.

Indexed as

DNA-Binding ProteinsRNA-Binding ProteinsRNA, Long NoncodingTumor Suppressor p53-Binding Protein 1DNA Breaks, Double-StrandedDNA RepairGenomic InstabilityHEK293 CellsHumansProtein BindingTumor Suppressor Protein p53DNA-Binding ProteinsNEAT1 long non-coding RNA, humanNUDT16L1 protein, humanRNA-Binding ProteinsRNA, Long NoncodingTARDBP protein, humanTP53BP1 protein, humanTumor Suppressor p53-Binding Protein 1Tumor Suppressor Protein p53

Identifiers

PMID39349456
PMCPMC11443056

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.