Evidence map›Paper›PMID 35732114›Full record

ArticleCell reports2022

Dynamics and functional roles of splicing factor autoregulation.

Fangyuan Ding, Christina J Su, KeHuan Kuo Edmonds, Guohao Liang, Michael B Elowitz

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

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  20. Interplays betweenInternational journal of molecular sciences · 2023
    Article
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

5 authors at 2 institutions in 1 country.

Fangyuan DingDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA; Center for Synthetic Biology, Center for Complex Biological Systems, Chao Family Comprehensive Cancer Center, Department of Developmental and Cell Biology, and Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: dingfy@uci.edu.
Christina J SuDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
KeHuan Kuo EdmondsDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Guohao LiangDepartment of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Michael B ElowitzDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute. Electronic address: melowitz@caltech.edu.
California Institute of Technology · USUniversity of California, Irvine · US

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Howard Hughes Medical InstituteNIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Non-core spliceosome components are essential, conserved regulators of alternative splicing. They provide concentration-dependent control of diverse pre-mRNAs. Many splicing factors direct unproductive splicing of their own pre-mRNAs through negative autoregulation. However, the impact of such feedback loops on splicing dynamics at the single-cell level remains unclear. Here, we developed a system to quantitatively analyze negative autoregulatory splicing dynamics by splicing factor SRSF1 in response to perturbations in single HEK293 cells. We show that negative autoregulatory splicing provides critical functions for gene regulation, establishing a ceiling of SRSF1 protein concentration, reducing cell-cell heterogeneity in SRSF1 levels, and buffering variation in transcription. Most important, it adapts SRSF1 splicing activity to variations in demand from other pre-mRNA substrates. A minimal mathematical model of autoregulatory splicing explains these experimentally observed features and provides values for effective biochemical parameters. These results reveal the unique functional roles that splicing negative autoregulation plays in homeostatically regulating transcriptional programs.

Indexed as

Alternative SplicingRNA PrecursorsHEK293 CellsHomeostasisHumansRNA Splicing FactorsSerine-Arginine Splicing FactorsRNA PrecursorsRNA Splicing FactorsSerine-Arginine Splicing FactorsSRSF1 protein, humanbiological noiseCP: Molecular biologyfeedback adaptationfeedback dynamicslabel-free single-cell movie trackingmathematical modelnegative autoregulatory splicing

Identifiers

PMID35732114
PMCPMC9262138
OpenAlexW4283274383

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.