Evidence map›Paper›PMID 27485701›Full record

ArticleScientific reports2016

Interference in transcription of overexpressed genes by promoter-proximal downstream sequences.

A Turchinovich, H M Surowy, A G Tonevitsky, B Burwinkel

Open access · goldAbstract read
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Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

4 citing papers in PubMed, 9 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

4 authors at 2 institutions in 2 countries.

A TurchinovichMolecular Epidemiology C080, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, Germany.
H M SurowyMolecular Epidemiology C080, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, Germany.
A G TonevitskyP. Hertsen Moscow Oncology Research Institute, National Center of Medical Radiological Research, 3 Second Botkinsky Lane, Moscow, 125284, Russia.
B BurwinkelMolecular Epidemiology C080, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, Germany.
German Cancer Research Center · DEP.A. Hertzen Moscow Oncology Research Institute · RU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite a high sequence homology among four human RNAi-effectors Argonaute proteins and their coding sequences, the efficiency of ectopic overexpression of AGO3 and AGO4 coding sequences in human cells is greatly reduced as compared to AGO1 and AGO2. While investigating this phenomenon, we documented the existence of previously uncharacterized mechanism of gene expression regulation, which is manifested in greatly varying basal transcription levels from the RNApolII promoters depending on the promoter-proximal downstream sequences. Specifically, we show that distinct overexpression of Argonaute coding sequences cannot be explained by mRNA degradation in the cytoplasm or nucleus, and exhibits on transcriptional level. Furthermore, the first 1000-2000 nt located immediately downstream the promoter had the most critical influence on ectopic gene overexpression. The transcription inhibiting effect, associated with those downstream sequences, subsided with increasing distance to the promoter and positively correlated with promoter strength. We hypothesize that the same mechanism, which we named promoter proximal inhibition (PPI), could generally contribute to basal transcription levels of genes, and could be mainly responsible for the essence of difficult-to-express recombinant proteins. Finally, our data reveal that expression of recombinant proteins in human cells can be greatly enhanced by using more permissive promoter adjacent downstream sequences.

Indexed as

Transcription, GeneticArgonaute ProteinsCell LineGene Expression RegulationHeLa CellsHumansMCF-7 CellsPromoter Regions, GeneticRNA, MessengerRNA Polymerase IIRNA StabilityArgonaute ProteinsRNA, MessengerRNA Polymerase II

Identifiers

PMID27485701
PMCPMC4971500
OpenAlexW2477068541

What OpenQuestion holds

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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.