How the initiating ribosome copes with ppGpp to translate mRNAs

PLoS Biology
Daria S VinogradovaPohl Milon

Abstract

During host colonization, bacteria use the alarmones (p)ppGpp to reshape their proteome by acting pleiotropically on DNA, RNA, and protein synthesis. Here, we elucidate how the initiating ribosome senses the cellular pool of guanosine nucleotides and regulates the progression towards protein synthesis. Our results show that the affinity of guanosine triphosphate (GTP) and the inhibitory concentration of ppGpp for the 30S-bound initiation factor IF2 vary depending on the programmed mRNA. The TufA mRNA enhanced GTP affinity for 30S complexes, resulting in improved ppGpp tolerance and allowing efficient protein synthesis. Conversely, the InfA mRNA allowed ppGpp to compete with GTP for IF2, thus stalling 30S complexes. Structural modeling and biochemical analysis of the TufA mRNA unveiled a structured enhancer of translation initiation (SETI) composed of two consecutive hairpins proximal to the translation initiation region (TIR) that largely account for ppGpp tolerance under physiological concentrations of guanosine nucleotides. Furthermore, our results show that the mechanism enhancing ppGpp tolerance is not restricted to the TufA mRNA, as similar ppGpp tolerance was found for the SETI-containing Rnr mRNA. Finally, we show that I...Continue Reading

References

Jan 1, 1984·Molecular & General Genetics : MGG·A M RojasC G Kurland
Feb 1, 1980·European Journal of Biochemistry·K van der LakenP H van Knippenberg
Mar 8, 1996·Journal of Molecular Biology·Anna La TeanaClaudio O Gualerzi
Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Aug 29, 2006·Journal of Molecular Biology·Enrico CasertaClaudio O Gualerzi
Sep 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Pohl MilonClaudio O Gualerzi
Dec 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefan Duhr, Dieter Braun
Apr 22, 2008·Nucleic Acids Research·Andreas R GruberIvo L Hofacker
Apr 24, 2008·Molecular Microbiology·Matthew F TraxlerTyrrell Conway
May 29, 2010·Microbiology and Molecular Biology Reviews : MMBR·Zachary D DalebrouxMichele S Swanson
Oct 16, 2010·Environmental Microbiology·Katarzyna PotrykusM Cashel
Feb 18, 2012·Nature Reviews. Microbiology·Zachary D Dalebroux, Michele S Swanson
Apr 28, 2012·Nucleic Acids Research·Mariusz PopendaRyszard W Adamiak
May 9, 2012·Nature Structural & Molecular Biology·Pohl MilonMarina V Rodnina
Jun 23, 2012·Nucleic Acids Research·Attilio FabbrettiClaudio O Gualerzi
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Oct 2, 2013·Journal of the American Chemical Society·Joerg MittelstaetMarina V Rodnina
Apr 9, 2015·Nature Reviews. Microbiology·Vasili HauryliukKenn Gerdes
Aug 12, 2015·Cellular and Molecular Life Sciences : CMLS·Claudio O Gualerzi, Cynthia L Pon
Sep 5, 2015·Nucleic Acids Research·Akanksha GoyalMarina V Rodnina
Dec 8, 2015·Nature Biotechnology·Alexander SchmidtMatthias Heinemann
Feb 5, 2016·Molecular Microbiology·Ragnhild Bager SkjerningDavid J Clarke
Mar 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Rebecca M CorriganAngelika Gründling
May 21, 2016·Science·Venu KamarthapuEvgeny Nudler
Sep 25, 2016·Microbiological Research·Xiaohui XuXiaomei Hu
Dec 17, 2016·Science·Alexander HarmsKenn Gerdes
Dec 19, 2018·Nature Chemical Biology·Boyuan WangMichael T Laub
Apr 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Patricia Sanchez-VazquezRichard L Gourse
Aug 28, 2019·Talanta·Eva ZborníkováDominik Rejman

Citations

Mar 17, 2020·PLoS Genetics·Heinrich SchäferKürşad Turgay
Jun 11, 2020·The Journal of Biological Chemistry·Rodney Tollerson, Michael Ibba
Nov 6, 2020·Nature Reviews. Microbiology·Sophie E IrvingRebecca M Corrigan
Feb 9, 2021·Frontiers in Microbiology·Mikel Irastortza-Olaziregi, Orna Amster-Choder
Feb 16, 2021·Frontiers in Microbiology·He Cheng-Guang, Claudio O Gualerzi
Nov 10, 2020·Frontiers in Microbiology·Llorenç Fernández-Coll, M Cashel

Related Concepts

DNA
Guanosine Pentaphosphate
Guanosine Tetraphosphate
Guanosine Triphosphate
Nucleotides
Ribosomes
RNA
RNA, Messenger
Prokaryotic Initiation Factor-2
Proximal

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.

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.

Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, but also fevers and skin rashes. Here is the latest on this disease.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

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.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.

Cell Atlas Along the Gut-Brain Axis

Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.

Chronic Traumatic Encephalopathy

Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that occurs in individuals that suffer repetitive brain trauma. Discover the latest research on traumatic encephalopathy here.

Related Papers

BioRxiv : the Preprint Server for Biology
Daria S VinogradovaPohl Milon
Proceedings of the National Academy of Sciences of the United States of America
Pohl MilonClaudio O Gualerzi
Biochimica Et Biophysica Acta
A Simoncsits, J Tomasz
© 2021 Meta ULC. All rights reserved