Single-cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction

Molecular Systems Biology
Andrzej J RzepielaMihaela Zavolan

Abstract

miRNAs are small RNAs that regulate gene expression post-transcriptionally. By repressing the translation and promoting the degradation of target mRNAs, miRNAs may reduce the cell-to-cell variability in protein expression, induce correlations between target expression levels, and provide a layer through which targets can influence each other's expression as "competing RNAs" (ceRNAs). However, experimental evidence for these behaviors is limited. Combining mathematical modeling with RNA sequencing of individual human embryonic kidney cells in which the expression of two distinct miRNAs was induced over a wide range, we have inferred parameters describing the response of hundreds of miRNA targets to miRNA induction. Individual targets have widely different response dynamics, and only a small proportion of predicted targets exhibit high sensitivity to miRNA induction. Our data reveal for the first time the response parameters of the entire network of endogenous miRNA targets to miRNA induction, demonstrating that miRNAs correlate target expression and at the same time increase the variability in expression of individual targets across cells. The approach is generalizable to other miRNAs and post-transcriptional regulators to impro...Continue Reading

References

Feb 17, 2005·Genes & Development·Chryssa KanellopoulouKlaus Rajewsky
Aug 17, 2005·PLoS Computational Biology·Dominic GrünNikolaus Rajewsky
Sep 9, 2005·Nucleic Acids Research·Georg W BornkammJean Feuillard
Nov 26, 2005·Science·Kyle Kai-How FarhDavid P Bartel
Jun 1, 2006·Nature Genetics·Eran Hornstein, Noam Shomron
Mar 3, 2007·BMC Bioinformatics·Dimos GaidatzisMihaela Zavolan
Aug 24, 2007·PLoS Biology·Erel LevineTerence Hwa
Nov 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Vahid Shahrezaei, Peter S Swain
Jan 20, 2011·Nature Reviews. Genetics·Eric Huntzinger, Elisa Izaurralde
Mar 23, 2011·PLoS Computational Biology·Matteo OsellaMichele Caselle
Aug 23, 2011·Nature Genetics·Shankar MukherjiAlexander van Oudenaarden
Sep 13, 2011·Nature Structural & Molecular Biology·David M GarciaDavid P Bartel
May 1, 2012·Cell·Margaret S Ebert, Phillip A Sharp
Oct 2, 2012·Methods : a Companion to Methods in Enzymology·Lukasz JaskiewiczMihaela Zavolan
Mar 1, 2013·Nature·Thomas B HansenJørgen Kjems
Mar 1, 2013·Nature·Sebastian MemczakNikolaus Rajewsky
Mar 12, 2013·Biophysical Journal·Matteo FigliuzziAndrea De Martino
Jul 11, 2013·PloS One·Carla BosiaRiccardo Zecchina
Nov 29, 2013·Epigenomics·Andreas J Gruber, Mihaela Zavolan
Dec 5, 2013·Molecular Systems Biology·Jean HausserMihaela Zavolan
Mar 29, 2014·Genome Research·Florian ErhardRalf Zimmer
Apr 22, 2014·Nature Methods·Dominic GrünAlexander van Oudenaarden
Jul 16, 2014·Nature Reviews. Genetics·Jean Hausser, Mihaela Zavolan
Jan 23, 2015·Molecular Biology of the Cell·Souvik GhoshSuvendra N Bhattacharyya
Apr 4, 2015·Science·Jörn M SchmiedelAlexander van Oudenaarden
Jun 17, 2015·Methods : a Companion to Methods in Enzymology·Brian MunskyGregor Neuert

❮ Previous
Next ❯

Citations

Nov 2, 2019·PLoS Computational Biology·Mattia MiottoAndrea De Martino
Mar 3, 2020·Frontiers in Immunology·Kaycie S LawsonJerome E Groopman
Dec 19, 2020·Wiley Interdisciplinary Reviews. RNA·Austin M GowenSowmya V Yelamanchili
Apr 8, 2020·Computational and Structural Biotechnology Journal·Elsi FerroCarla Bosia
Oct 30, 2020·Nature Communications·Marcel TarbierMarc R Friedländer
Apr 21, 2021·Epigenomics·Huanhou SuLijing Wang

❮ Previous
Next ❯

Datasets Mentioned

BETA
SRP067502
SRP150046

Methods Mentioned

BETA
transfection
immunoprecipitation
FCS
PCRs
PCR
Chip
in vitro transcription
Assay
CLIP

Software Mentioned

TargetScan
Cellranger
StochKit
PAGODA
MIRZA
Illumina
GOstats
R Bioconductor
Genomics
Demultiplexing

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.