Mechanism of ribosome stalling during translation of a poly(A) tail

Nature Structural & Molecular Biology
Viswanathan ChandrasekaranRamanujan S Hegde


Faulty or damaged messenger RNAs are detected by the cell when translating ribosomes stall during elongation and trigger pathways of mRNA decay, nascent protein degradation and ribosome recycling. The most common mRNA defect in eukaryotes is probably inappropriate polyadenylation at near-cognate sites within the coding region. How ribosomes stall selectively when they encounter poly(A) is unclear. Here, we use biochemical and structural approaches in mammalian systems to show that poly-lysine, encoded by poly(A), favors a peptidyl-transfer RNA conformation suboptimal for peptide bond formation. This conformation partially slows elongation, permitting poly(A) mRNA in the ribosome's decoding center to adopt a ribosomal RNA-stabilized single-stranded helix. The reconfigured decoding center clashes with incoming aminoacyl-tRNA, thereby precluding elongation. Thus, coincidence detection of poly-lysine in the exit tunnel and poly(A) in the decoding center allows ribosomes to detect aberrant mRNAs selectively, stall elongation and trigger downstream quality control pathways essential for cellular homeostasis.


Jan 16, 1999·Nucleic Acids Research·J H GraberT F Smith
Oct 9, 2002·Nature·Malcolm J GardnerBart Barrell
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Mar 25, 2005·Nucleic Acids Research·Pierre MignonPaul Geerlings
Sep 30, 2008·Journal of Molecular Biology·Jianli Lu, Carol Deutsch
Feb 11, 2009·The Journal of Biological Chemistry·Lyudmila N DimitrovaToshifumi Inada
Oct 20, 2009·Nature·T Martin Schmeing, V Ramakrishnan
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 27, 2010·Methods in Molecular Biology·Ajay SharmaRamanujan S Hegde
Sep 14, 2010·Nature·Mario H Bengtson, Claudio A P Joazeiro
May 31, 2011·Nature Structural & Molecular Biology·Thomas BeckerRoland Beckmann
Sep 10, 2011·Trends in Biochemical Sciences·Ambro van Hoof, Eric J Wagner
Jun 6, 2012·Nature Structural & Molecular Biology·Christopher J Shoemaker, Rachel Green
Jan 8, 2013·Molecular Cell·Reut ShalgiChristopher B Burge
Jan 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Swati MandalMyung Hee Park
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Quentin DefenouillèreMicheline Fromont-Racine
Apr 26, 2013·Nature·Vicent PelechanoLars M Steinmetz
Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Florian Cymer, Gunnar von Heijne
Oct 5, 2013·Trends in Genetics : TIG·Bijoyita Roy, Allan Jacobson
Apr 1, 2014·Cell·Suzanne WolffAndrew Dillin
Feb 20, 2015·ELife·Kristin S KoutmouRachel Green
Mar 19, 2015·Annual Review of Biochemistry·Johnathan Labbadia, Richard I Morimoto
Aug 19, 2015·Journal of Structural Biology·Alexis Rohou, Nikolaus Grigorieff
Sep 1, 2015·Science Advances·Laura ArthurSergej Djuranovic
Dec 3, 2015·Trends in Biochemical Sciences·Sichen Shao, Ramanujan S Hegde
Feb 10, 2016·Current Opinion in Structural Biology·Daniel N WilsonRoland Beckmann
Jul 2, 2016·Science·David BalchinF Ulrich Hartl
Jul 5, 2016·Cell·Caitlin E GambleElizabeth J Grayhack

❮ Previous
Next ❯


Mar 24, 2020·Nature Structural & Molecular Biology·Yoshitaka MatsuoToshifumi Inada
Jun 11, 2020·The Journal of Cell Biology·Stephanie L MoonRoy Parker
May 30, 2020·ELife·Slavica Pavlovic DjuranovicSergej Djuranovic
Jun 23, 2020·Annual Review of Biochemistry·Cole S Sitron, Onn Brandman
Apr 17, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Terence T L Tang, Lori A Passmore
Aug 17, 2020·The Biochemical Journal·Rodrigo D RequiãoFernando L Palhano
Jul 28, 2020·Nucleic Acids Research·Kathleen L McCannTraci M Tanaka Hall
Oct 13, 2020·Current Genetics·Sezen Meydan, Nicholas R Guydosh
Nov 28, 2020·Science·Nirupa DesaiV Ramakrishnan
Nov 29, 2020·Journal of Cell Science·Ben P Phillips, Elizabeth A Miller
Jul 21, 2020·Current Opinion in Structural Biology·Kyle T PowersChristiane Schaffitzel
Feb 18, 2021·ELife·Luca MinatiMassimiliano Clamer
Mar 14, 2021·Molecular Cell·Karole N D'Orazio, Rachel Green
Mar 29, 2021·The Journal of Biological Chemistry·Géssica C BarrosFernando L Palhano
Apr 29, 2021·Molecular Cell·Anna ThrunClaudio A P Joazeiro
May 6, 2021·Wiley Interdisciplinary Reviews. RNA·Christelle MorrisEmiliano P Ricci
May 11, 2021·Trends in Biochemical Sciences·Matthew C J Yip, Sichen Shao
Jun 1, 2021·NAR Genomics and Bioinformatics·Katarzyna ChyżyńskaEivind Valen
Jun 12, 2021·Frontiers in Molecular Biosciences·Jiří KoubekGünter Kramer
Jun 23, 2021·Nucleic Acids Research·Kyle T PowersChristiane Schaffitzel

❮ Previous
Next ❯

Related Concepts

Trending Feeds


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.

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.

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.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies 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.


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.

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.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.