Loss of mRNA surveillance pathways results in widespread protein aggregation.

Scientific Reports
Nur H JamarChris M Grant

Abstract

Eukaryotic cells contain translation-associated mRNA surveillance pathways which prevent the production of potentially toxic proteins from aberrant mRNA translation events. We found that loss of mRNA surveillance pathways in mutants deficient in nonsense-mediated decay (NMD), no-go decay (NGD) and nonstop decay (NSD) results in increased protein aggregation. We have isolated and identified the proteins that aggregate and our bioinformatic analyses indicates that increased aggregation of aggregation-prone proteins is a general occurrence in mRNA surveillance mutants, rather than being attributable to specific pathways. The proteins that aggregate in mRNA surveillance mutants tend to be more highly expressed, more abundant and more stable proteins compared with the wider proteome. There is also a strong correlation with the proteins that aggregate in response to nascent protein misfolding and an enrichment for proteins that are substrates of ribosome-associated Hsp70 chaperones, consistent with susceptibility for aggregation primarily occurring during translation/folding. We also identified a significant overlap between the aggregated proteins in mRNA surveillance mutants and ageing yeast cells suggesting that translation-depende...Continue Reading

References

Feb 26, 2000·Annual Review of Genetics·P Hilleren, R Parker
Feb 24, 2001·Cell·L E Maquat, G G Carmichael
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·E W TrotterJ V Gray
Oct 17, 2003·Nature·Sina GhaemmaghamiJonathan S Weissman
May 7, 2004·The Journal of Biological Chemistry·Ronnie LumJohn R Glover
Jun 4, 2005·Nature Structural & Molecular Biology·Milo B Fasken, Anita H Corbett
Dec 20, 2005·Journal of Molecular Biology·Frederic RousseauJoost W H Schymkowitz
Apr 10, 2007·Trends in Biochemical Sciences·Gian Gaetano TartagliaMichele Vendruscolo
Oct 21, 2009·Nature Chemical Biology·Lila M Gierasch, Anne Gershenson
Apr 7, 2010·The Journal of Cell Biology·Ansgar KoplinElke Deuerling
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Robin E C LeeLynn A Megeney
Dec 3, 2010·Cold Spring Harbor Perspectives in Biology·R Martin VabulasF Ulrich Hartl
Feb 10, 2012·Current Opinion in Structural Biology·Michele Vendruscolo
Jun 6, 2012·Nature Structural & Molecular Biology·Christopher J Shoemaker, Rachel Green
Jun 29, 2012·Wiley Interdisciplinary Reviews. RNA·A Alejandra Klauer, Ambro van Hoof
Sep 5, 2012·Journal of Cell Science·Therese JacobsonMarkus J Tamás
Oct 13, 2012·Annual Review of Cell and Developmental Biology·Jeremy D O'ConnellEdward M Marcotte
Oct 26, 2012·Molecular Biology of the Cell·Theodore W PetersRobert E Hughes
Jan 16, 2014·Journal of Cell Science·Alan J Weids, Chris M Grant
Jun 21, 2014·Trends in Cell Biology·Mark S HippF Ulrich Hartl
Jun 28, 2014·Biomolecules·Markus J TamásPhilipp Christen
Dec 4, 2014·Cell Reports·Romain ChristianoTobias C Walther
Dec 9, 2014·Mutation Research. Reviews in Mutation Research·Jake N Miller, David A Pearce
Nov 7, 2015·Trends in Biochemical Sciences·Kevin W TippingSheena E Radford
Apr 19, 2016·Scientific Reports·Alan J WeidsChris M Grant
Jan 1, 2015·Journal of Neuromuscular Diseases·Juliane S MüllerRita Horvath
Jan 20, 2017·Open Biology·Tobias von der HaarCampbell W Gourlay
Apr 18, 2017·Mechanisms of Ageing and Development·Yulia Gonskikh, Norbert Polacek
May 5, 2017·Nucleic Acids Research·Nur H JamarChris M Grant
Jun 21, 2017·The Journal of Cell Biology·Norfadilah HamdanChris M Grant

❮ Previous
Next ❯

Citations

Jul 18, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Anastasia S OchkasovaGalina G Karpova
Oct 1, 2021·Molecular Neurobiology·Ribhav MishraAmit Mishra

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination

Software Mentioned

Mascot
Softworx
GraphPad Prism
FunCat
MIPS
Scaffold

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.