Evidence map›Paper›PMID 31811203›Full record

ArticleScientific reports2019

A negative feedback mechanism links UBC gene expression to ubiquitin levels by affecting RNA splicing rather than transcription.

Marzia Bianchi, Rita Crinelli, Elisa Giacomini, Elisa Carloni, Lucia Radici, Emanuele-Salvatore Scarpa, Filippo Tasini, Mauro Magnani

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

22 citing papers in PubMed, 32 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

8 authors at 1 institution in 1 country.

Marzia BianchiDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy. marzia.bianchi@uniurb.it.
Rita CrinelliDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Elisa GiacominiDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Elisa CarloniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Lucia RadiciDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Emanuele-Salvatore ScarpaDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Filippo TasiniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
Mauro MagnaniDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, PU, Italy.
University of Urbino · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

UBC gene plays a critical role in maintaining ubiquitin (Ub) homeostasis. It is upregulated under stress conditions, and herein we report that it is downregulated upon Ub overexpression. Downregulation occurs in a dose-dependent manner, suggesting the existence of a fine-tuned Ub sensing mechanism. This "sensor" requires a conjugation competent ubiquitin to detect Ub levels. Searching the sensor among the transcription factors involved in basal and stress-induced UBC gene expression was unsuccessful. Neither HSF1 and HSF2, nor Sp1 and YY1 are affected by the increased Ub levels. Moreover, mutagenesis of their binding sites in the UBC promoter-driven reporter constructs does not impair the downmodulation effect. Epigenetic studies show that H2A and H2B ubiquitination within the UBC promoter region is unchanged upon ubiquitin overexpression. Noteworthy, quantification of nascent RNA molecules excludes that the downmodulation arises in the transcription initiation step, rather pointing towards a post-transcriptional mechanism. Indeed, a significantly higher fraction of unspliced UBC mRNA is detected in ubiquitin overexpressing cells, compared to empty vector transfected cells. Our findings suggest how increasing cellular ubiquitin levels may control the expression of UBC gene by negatively affecting the splicing of its pre-mRNA, providing a straightforward feedback strategy for the homeostatic control of ubiquitin pools.

Indexed as

Feedback, PhysiologicalRNA SplicingBinding SitesGene Expression RegulationHeLa CellsHumansPromoter Regions, GeneticRNA, MessengerRNA PrecursorsTranscription, GeneticUbiquitin CRNA, MessengerRNA PrecursorsUbiquitin C

Identifiers

PMID31811203
PMCPMC6898720
OpenAlexW2993321646

What OpenQuestion holds

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LicenceCC BY
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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.