Evidence map›Paper›PMID 39005384›Full record

ArticlebioRxiv : the preprint server for biology2024

TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.

Megan M Dykstra, Kaitlin Weskamp, Nicolás B Gómez, Jacob Waksmacki, Elizabeth Tank, M Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li and 15 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Megan M DykstraNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI.ORCID 0000-0002-4551-2478
Kaitlin WeskampChemistry Department, Nebraska Wesleyan University, Lincoln, NE.
Nicolás B GómezGraduate Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, MI.
Jacob WaksmackiDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Elizabeth TankDepartment of Neurology, University of Michigan, Ann Arbor, MI.
M Rebecca GlineburgBiological Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA.
Allison SnyderNeurogenetics Branch, NINDS, NIH, Bethesda, MD.
Emile PinarbasiDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Michael BekierDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Xingli LiDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Jen BaiDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Shameena ShahzadDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Juno NedumaranDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Clare WielandNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI.
Corey StewartNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI.
Sydney WilleyNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI.
Nikolas GrotewoldMedical Scientist Training Program, University of Michigan, Ann Arbor, MI.
Jonathon McBrideDepartment of Anesthesiology, University of Michigan, Ann Arbor, MI.
John J MoranAtlanta Pediatric Research Alliance, Emory University, Atlanta, GA.
Aditya V SuryakumarDepartment of Neurology, University of Michigan, Ann Arbor, MI.
Michael LucasDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI.
Peter TessierDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI.
Michael WardNeurogenetics Branch, NINDS, NIH, Bethesda, MD.ORCID 0000-0002-5296-8051
Peter ToddNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI.ORCID 0000-0003-4781-6376
Sami J BarmadaNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI.

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kelly Bakulski · 2021 to 2026
$26.5M
Mechanisms of inherited neurodegenerative diseasesZIANS003155 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI WARD, MICHAEL · 2016 to 2025
$24.7M
Hexanucleotide repeat translation in ALS and Frontotemporal DementiaR01NS099280 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Peter K Todd · 2016 to 2026
$4.9M
Cellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1M
RNA decay in amyotrophic lateral sclerosis and frontotemporal lobar degenerationR01NS097542 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2016 to 2025
$3.8M
Atypical TDP43 isoforrms driving neurodegeneration in FTD/ALSR01NS113943 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2020 to 2024
$1.9M
Spatiotemporal analysis of TDP-43 toxicity and endolysosomal turnover mechanismsR56NS128110 · NINDS · UNIVERSITY OF ARIZONA · PI BARMADA, SAMI, BUCHAN, JOHN ROSS · 2022 to 2022
$393k
Identifying the function of alternatively spliced TDP43 isoforms and contribution to diseaseF31NS134123 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DYKSTRA, MEGAN · 2023 to 2024
$83k
Investigating the mechanism of UPF1-mediated rescue of TDP-43-based models of ALS and FTDF31NS115257 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GOMEZ, NICOLAS BENJAMIN · 2019 to 2021
$76k
Bypassing cellular stress pathways in frontotemporal dementia and ALSI01BX004842 · VA · VETERANS HEALTH ADMINISTRATION · PI TODD, PETER K · 2020 to 2023
–
BLRD VA I01 BX004842NIA NIH HHS P30 AG072931NIGMS NIH HHS T32 GM007863NIGMS NIH HHS T32 GM145470NINDS NIH HHS F31 NS115257NINDS NIH HHS F31 NS134123NINDS NIH HHS R01 NS097542NINDS NIH HHS R01 NS099280NINDS NIH HHS R01 NS113943NINDS NIH HHS R56 NS128110
6 · The paper itself

Abstract

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, highly prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a byproduct of TDP43 autoregulation and cleared by nonsense mediated RNA decay (NMD). The sTDP43-encoding transcripts that escape NMD can lead to toxicity but are rapidly degraded post-translationally. Circumventing these regulatory mechanisms by overexpressing sTDP43 results in neurodegeneration

Identifiers

PMID39005384
PMCPMC11244999

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.