Evidence map›Paper›PMID 37904984›Full record

ArticlebioRxiv : the preprint server for biology2023

CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.

Rachel Anderson, Michael Das, Yeonji Chang, Kelsey Farenhem, Ankur Jain

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Rachel AndersonWhitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Michael DasWhitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Yeonji ChangWhitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Kelsey FarenhemWhitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Ankur JainWhitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Whitehead Institute for Biomedical Research · US

Funding

RNA Gelation in Repeat Expansion DisordersR00AG053434 · NIA · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAIN, ANKUR · 2018 to 2020
$861k
NIA NIH HHS R00 AG053434
6 · The paper itself

Abstract

Expansions of CAG trinucleotide repeats cause several rare neurodegenerative diseases. The disease-causing repeats are translated in multiple reading frames, without an identifiable initiation codon. The molecular mechanism of this repeat-associated non-AUG (RAN) translation is not known. We find that expanded CAG repeats create new splice acceptor sites. Splicing of proximal donors to the repeats produces unexpected repeat-containing transcripts. Upon splicing, depending on the sequences surrounding the donor, CAG repeats may become embedded in AUG-initiated open reading frames. Canonical AUG-initiated translation of these aberrant RNAs accounts for proteins that are attributed to RAN translation. Disruption of the relevant splice donors or the in-frame AUG initiation codons is sufficient to abrogate RAN translation. Our findings provide a molecular explanation for the abnormal translation products observed in CAG trinucleotide repeat expansion disorders and add to the repertoire of mechanisms by which repeat expansion mutations disrupt cellular functions.

Identifiers

PMID37904984
PMCPMC10614865
OpenAlexW4387704286

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.