Translation efficiency is a determinant of the magnitude of miRNA-mediated repression

Scientific Reports
Kyle A CottrellSergej Djuranovic

Abstract

MicroRNAs are well known regulators of mRNA stability and translation. However, the magnitude of both translational repression and mRNA decay induced by miRNA binding varies greatly between miRNA targets. This can be the result of cis and trans factors that affect miRNA binding or action. We set out to address this issue by studying how various mRNA characteristics affect miRNA-mediated repression. Using a dual luciferase reporter system, we systematically analyzed the ability of selected mRNA elements to modulate miRNA-mediated repression. We found that changing the 3'UTR of a miRNA-targeted reporter modulates translational repression by affecting the translation efficiency. This 3'UTR dependent modulation can be further altered by changing the codon-optimality or 5'UTR of the luciferase reporter. We observed maximal repression with intermediate codon optimality and weak repression with very high or low codon optimality. Analysis of ribosome profiling and RNA-seq data for endogenous miRNA targets revealed translation efficiency as a key determinant of the magnitude of miRNA-mediated translational repression. Messages with high translation efficiency were more robustly repressed. Together our results reveal modulation of miRNA-...Continue Reading

References

May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·M Kozak
Jan 1, 1996·Molecular and Cellular Biology·R L Tanguay, D R Gallie
Aug 5, 2003·Nature Reviews. Genetics·Scott Kuersten, Elizabeth B Goodwin
Dec 19, 2003·Nucleic Acids Research·Donna KarolchikW James Kent
Sep 28, 2004·Nucleic Acids Research·Mario dos ReisLorenz Wernisch
Mar 22, 2005·Gene·Michele IaconoGraziano Pesole
Jul 4, 2006·Genes & Development·Isabelle Behm-AnsmantElisa Izaurralde
Apr 28, 2007·Science·To-Ha ThaiKlaus Rajewsky
Apr 28, 2007·Science·Antony RodriguezAllan Bradley
Sep 26, 2007·Nature Genetics·Michael KerteszEran Segal
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Esmerina TiliCarlo Maria Croce
Jan 15, 2008·Cell·Ana EulalioElisa Izaurralde
Aug 1, 2008·Nature·Matthias SelbachNikolaus Rajewsky
Nov 6, 2008·Nucleic Acids Research·Patricia P Chan, Todd M Lowe
Nov 13, 2008·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Lioudmila V SharovaMinoru S H Ko
Nov 26, 2008·RNA·Ana EulalioElisa Izaurralde
Feb 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Maurizio CeppiPhilippe Pierre
Apr 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sarah E CalvoVamsi K Mootha
Jun 11, 2010·Annual Review of Biochemistry·Marc Robert FabianWitold Filipowicz
Sep 13, 2011·Nature Structural & Molecular Biology·David M GarciaDavid P Bartel
Oct 11, 2011·Molecular Cell·Joerg E BraunElisa Izaurralde
Nov 26, 2011·Algorithms for Molecular Biology : AMB·Ronny LorenzIvo L Hofacker
Feb 22, 2012·Genes & Development·Wayne O MilesNicholas J Dyson
Mar 1, 2012·Nucleic Acids Research·Pradipta KunduWitold Filipowicz
Jun 6, 2012·Nature Structural & Molecular Biology·Marc R Fabian, Nahum Sonenberg
Jun 14, 2012·Comparative and Functional Genomics·Patricia R AraujoLuiz O F Penalva
Aug 28, 2012·Trends in Genetics : TIG·Eva Maria Novoa, Lluís Ribas de Pouplana
Nov 20, 2012·Nucleic Acids Research·Emiliano P RicciThéophile Ohlmann
Dec 5, 2012·Cold Spring Harbor Perspectives in Biology·John W B HersheyMichael B Mathews

❮ Previous
Next ❯

Citations

Feb 8, 2018·ELife·Seyed Mehdi JafarnejadNahum Sonenberg
Oct 17, 2018·The Journal of Clinical Investigation·Qingqing WeiZheng Dong
Feb 20, 2019·Molecular Systems Biology·Basak EraslanJulien Gagneur
Sep 19, 2019·RNA·Ashrut NarulaOlivia S Rissland
May 22, 2018·MicroRNA·Neetu Dahiya, Chintamani D Atreya
Apr 17, 2020·Frontiers in Cell and Developmental Biology·Tine TesovnikTadej Battelino
May 2, 2021·Computational Biology and Chemistry·Supriyo ChakrabortyArif Uddin
May 7, 2021·ELife·Sibylle Mitschka, Christine Mayr
Jun 18, 2021·Cell Systems·Nika ShakibaDomitilla Del Vecchio
Aug 28, 2021·Omics : a Journal of Integrative Biology·K J SindhuDevarajan Karunagaran

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE22004

Methods Mentioned

BETA
transfection
RNAseq
PCR
Assay
RNA-seq
immunoprecipitation

Software Mentioned

Vienna package
ggplot2
TargetScan
Eureqa
Ensembl
R
BioMart

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.