Evidence map›Paper›PMID 31291322›Full record

ArticlePloS one2019

The RNA encoding the microtubule-associated protein tau has extensive structure that affects its biology.

Jonathan L Chen, Walter N Moss, Adam Spencer, Peiyuan Zhang, Jessica L Childs-Disney, Matthew D Disney

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Jonathan L ChenDepartment of Chemistry, The Scripps Research Institute, Jupiter, Florida, United States of America.ORCID 0000-0001-7907-9732
Walter N MossRoy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, Iowa, United States of America.ORCID 0000-0001-6419-5570
Adam SpencerDepartment of Chemistry, The Scripps Research Institute, Jupiter, Florida, United States of America.
Peiyuan ZhangDepartment of Chemistry, The Scripps Research Institute, Jupiter, Florida, United States of America.
Jessica L Childs-DisneyDepartment of Chemistry, The Scripps Research Institute, Jupiter, Florida, United States of America.
Matthew D DisneyDepartment of Chemistry, The Scripps Research Institute, Jupiter, Florida, United States of America.ORCID 0000-0001-8486-1796
Scripps Research Institute · USIowa State University · US

Funding

Validation of r(G4C2)exp-binding small molecules in vivo and c9FTD/ALS biomarker developmentP01NS099114 · NINDS · UNIVERSITY OF FLORIDA · PI DISNEY, MATTHEW D, PETRUCELLI, LEONARD · 2017 to 2021
$6.5M
Using a disease-affected cell to synthesize its own drugDP1NS096898 · NINDS · SCRIPPS FLORIDA · PI DISNEY, MATTHEW D · 2015 to 2019
$5.0M
Sequence-based Design of Small Molecules Targeting RNAR01GM097455 · NIGMS · SCRIPPS FLORIDA · PI DISNEY, MATTHEW D · 2012 to 2019
$4.6M
Finding, folding and characterizing the functions of disease-relevant RNA structuresR01GM133810 · NIGMS · IOWA STATE UNIVERSITY · PI Walter Moss · 2019 to 2026
$2.8M
Understanding Epstein Barr virus oncogenicity through non-coding RNA structureR00GM112877 · NIGMS · IOWA STATE UNIVERSITY · PI MOSS, WALTER · 2017 to 2019
$747k
NIGMS NIH HHS R00 GM112877NIGMS NIH HHS R01 GM097455NIGMS NIH HHS R01 GM133810NINDS NIH HHS DP1 NS096898NINDS NIH HHS P01 NS099114
6 · The paper itself

Abstract

Tauopathies are neurodegenerative diseases that affect millions of people worldwide including those with Alzheimer's disease. While many efforts have focused on understanding the role of tau protein in neurodegeneration, there has been little done to systematically analyze and study the structures within tau's encoding RNA and their connection to disease pathology. Knowledge of RNA structure can provide insights into disease mechanisms and how to affect protein production for therapeutic benefit. Using computational methods based on thermodynamic stability and evolutionary conservation, we identified structures throughout the tau pre-mRNA, especially at exon-intron junctions and within the 5' and 3' untranslated regions (UTRs). In particular, structures were identified at twenty exon-intron junctions. The 5' UTR contains one structured region, which lies within a known internal ribosome entry site. The 3' UTR contains eight structured regions, including one that contains a polyadenylation signal. A series of functional experiments were carried out to assess the effects of mutations associated with mis-regulation of alternative splicing of exon 10 and to identify regions of the 3' UTR that contain cis-regulatory elements. These studies defined novel structural regions within the mRNA that affect stability and pre-mRNA splicing and may lead to new therapeutic targets for treating tau-associated diseases.

Indexed as

3' Untranslated RegionsAlternative SplicingAlzheimer DiseaseExonsHumansIntronsMutationNucleic Acid ConformationPolyadenylationRNA, MessengerRNA PrecursorsTauopathiestau Proteins3' Untranslated RegionsRNA, MessengerRNA Precursorstau Proteins

Identifiers

PMID31291322
PMCPMC6619747
OpenAlexW2957073438

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.