Evidence map›Paper›PMID 36414621›Full record

ArticleNature communications2022

Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS.

Richard Taylor, Fursham Hamid, Triona Fielding, Patricia M Gordon, Megan Maloney, Eugene V Makeyev, Corinne Houart

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026
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  18. RNA in axons, dendrites, synapses and beyond.Frontiers in molecular neuroscience · 2024
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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

7 authors at 1 institution in 1 country.

Richard TaylorCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK. richard.taylor@kcl.ac.uk.ORCID 0000-0002-4657-6799
Fursham HamidCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK.ORCID 0000-0002-6846-7382
Triona FieldingCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK.
Patricia M GordonCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK.
Megan MaloneyCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK.
Eugene V MakeyevCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK.ORCID 0000-0001-6034-6896
Corinne HouartCentre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK. corinne.houart@kcl.ac.uk.ORCID 0000-0002-2062-3964
King's College London · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M007103/1Biotechnology and Biological Sciences Research Council BB/P001599/1Medical Research Council MR/K50130X/1/Medical Research Council MR/T033126/1Wellcome TrustWellcome Trust WT 220861/Z/20/Z
6 · The paper itself

Abstract

Loss of SFPQ is a hallmark of motor degeneration in ALS and prevents maturation of motor neurons when occurring during embryogenesis. Here, we show that in zebrafish, developing motor neurons lacking SFPQ exhibit axon extension, branching and synaptogenesis defects, prior to degeneration. Subcellular transcriptomics reveals that loss of SFPQ in neurons produces a complex set of aberrant intron-retaining (IR) transcripts coding for neuron-specific proteins that accumulate in neurites. Some of these local IR mRNAs are prematurely terminated within the retained intron (PreT-IR). PreT-IR mRNAs undergo intronic polyadenylation, nuclear export, and localise to neurites in vitro and in vivo. We find these IR and PreT-IR mRNAs enriched in RNAseq datasets of tissue from patients with familial and sporadic ALS. This shared signature, between SFPQ-depleted neurons and ALS, functionally implicates SFPQ with the disease and suggests that neurite-centred perturbation of alternatively spliced isoforms drives the neurodegenerative process.

Indexed as

Amyotrophic Lateral SclerosisAnimalsAxonsHumansIntronsMotor NeuronsRNA, MessengerZebrafishRNA, Messenger

Identifiers

PMID36414621
PMCPMC9681851
OpenAlexW4309701391

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.