scholarly journals Phosphorylation of Ribosomal Protein S6 differentially affects mRNA translation based on ORF length

2021 ◽  
Author(s):  
Jonathan Bohlen ◽  
Aurelio A. Teleman
Keyword(s):  
Ribosomal Protein ◽  
Mrna Translation ◽  
Translation Efficiency ◽  
Post Translational Modification ◽  
Coding Sequences ◽  
Functional Consequence ◽  
Ribosomal Protein S6 ◽  
Dynamic View ◽  
Ribosome Footprinting ◽  
Rps6 Phosphorylation

ABSTRACTPhosphorylation of Ribosomal Protein S6 (RPS6) was the first post-translational modification of the ribosome to be identified and is a commonly-used readout for mTORC1 activity. Although the cellular and organismal functions of RPS6 phosphorylation are known, its molecular consequences on translation are less well understood. Here we use selective ribosome footprinting to analyze the location of ribosomes containing phosphorylated RPS6 on endogenous mRNAs in cells. We find that RPS6 becomes progressively dephosphorylated on ribosomes as they translate an mRNA. As a consequence, average RPS6 phosphorylation is higher on mRNAs with short coding sequences (CDSs) compared to mRNAs with long CDSs. In particular, ribosomes translating on the endoplasmic reticulum are more rapidly dephosphorylated than cytosolic ribosomes. Loss of RPS6 phosphorylation causes a correspondingly larger drop in translation efficiency of mRNAs with short CDSs than long CDSs. Interestingly, mRNAs with 5’ TOP motifs are translated well also in the absence of RPS6 phosphorylation despite short CDS lengths, suggesting they are translated via a different mode. In sum this provides a dynamic view of RPS6 phosphorylation on ribosomes as they translate mRNAs in different subcellular localizations and the functional consequence on translation.

scholarly journals Molecular mechanisms for the control of translation by insulin

1997 ◽  
Vol 328 (2) ◽  
pp. 329-341 ◽  
Author(s):  
G. Christopher PROUD ◽  
M. Richard DENTON
Keyword(s):  
Ribosomal Protein ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Chain Elongation ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Translation Factors ◽  
Specific Mrnas

Insulin acutely stimulates protein synthesis in mammalian cells, and this involves activation of the process of mRNA translation. mRNA translation is a complex multi-step process mediated by proteins termed translation factors. Several translation factors are regulated in response to insulin, often as a consequence of changes in their states of phosphorylation. The initiation factor eIF4E binds to the cap structure at the 5ʹ-end of the mRNA and mediates assembly of an initiation-factor complex termed eIF4F. Assembly of this complex can be regulated by eIF4E-binding proteins (4E-BPs), which inhibit eIF4F complex assembly. Insulin induces phosphorylation of the 4E-BPs, resulting in alleviation of the inhibition. This regulatory mechanism is likely to be especially important for the control of the translation of specific mRNAs whose 5ʹ-untranslated regions (5ʹ-UTRs) are rich in secondary structure. Translation of another class of mRNAs, those with 5ʹ-UTRs containing polypyrimidine tracts is also activated by insulin and this, like phosphorylation of the 4E-BPs, appears to involve the rapamycin-sensitive signalling pathway which leads to activation of the 70 kDa ribosomal protein S6 kinase (p70 S6 kinase) and the phosphorylation of the ribosomal protein S6. Overall stimulation of translation may involve activation of initiation factor eIF2B, which is required for all initiation events. This effect is dependent upon phosphatidylinositol 3-kinase and may involve the inactivation of glycogen synthase kinase-3 and consequent dephosphorylation of eIF2B, leading to its activation. Peptide-chain elongation can also be activated by insulin, and this is associated with the dephosphorylation and activation of elongation factor eEF2, probably as a consequence of the insulin-induced reduction in eEF2 kinase activity. Thus multiple signalling pathways acting on different steps in translation are involved in the activation of this process by insulin and lead both to general activation of translation and to the selective regulation of specific mRNAs.

scholarly journals Ribosomal Protein S6 Associates with Alphavirus Nonstructural Protein 2 and Mediates Expression from Alphavirus Messages

2006 ◽  
Vol 80 (15) ◽  
pp. 7729-7739 ◽  
Author(s):  
Stephanie A. Montgomery ◽  
Peter Berglund ◽  
Clayton W. Beard ◽  
Robert E. Johnston
Keyword(s):  
Ribosomal Protein ◽  
Nonstructural Protein ◽  
Cellular Proteins ◽  
Nonstructural Proteins ◽  
Replication Complex ◽  
Equine Encephalitis Virus ◽  
Nonstructural Protein 2 ◽  
Ribosomal Protein S6 ◽  
Cellular Translation ◽  
Rps6 Phosphorylation

ABSTRACT Although alphaviruses dramatically alter cellular function within hours of infection, interactions between alphaviruses and specific host cellular proteins are poorly understood. Although the alphavirus nonstructural protein 2 (nsP2) is an essential component of the viral replication complex, it also has critical auxiliary functions that determine the outcome of infection in the host. To gain a better understanding of nsP2 function, we sought to identify cellular proteins with which Venezuelan equine encephalitis virus nsP2 interacted. We demonstrate here that nsP2 associates with ribosomal protein S6 (RpS6) and that nsP2 is present in the ribosome-containing fractions of a polysome gradient, suggesting that nsP2 associates with RpS6 in the context of the whole ribosome. This result was noteworthy, since viral replicase proteins have seldom been described in direct association with components of the ribosome. The association of RpS6 with nsP2 was detected throughout the course of infection, and neither the synthesis of the viral structural proteins nor the presence of the other nonstructural proteins was required for RpS6 interaction with nsP2. nsP1 also was associated with RpS6, but other nonstructural proteins were not. RpS6 phosphorylation was dramatically diminished within hours after infection with alphaviruses. Furthermore, a reduction in the level of RpS6 protein expression led to diminished expression from alphavirus subgenomic messages, whereas no dramatic diminution in cellular translation was observed. Taken together, these data suggest that alphaviruses alter the ribosome during infection and that this alteration may contribute to differential translation of host and viral messages.

scholarly journals The Р60-S6K1 isoform of ribosomal protein S6 kinase 1 is a product of alternative mRNA translation

2018 ◽  
Vol 90 (4) ◽  
pp. 25-35 ◽  
Author(s):  
I. V. Zaiets ◽  
◽  
A. S. Sivchenko ◽  
A. I. Khoruzhenko ◽  
L. O. Savinska ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Mrna Translation ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Ribosomal Protein S6 Kinase

Glucose exerts a permissive effect on the regulation of the initiation factor 4E binding protein 4E-BP1

2001 ◽  
Vol 358 (2) ◽  
pp. 497-503 ◽  
Author(s):  
Jigna PATEL ◽  
Xuemin WANG ◽  
Christopher G. PROUD
Keyword(s):  
Amino Acids ◽  
Ribosomal Protein ◽  
Binding Protein ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Ribosomal Protein S6 ◽  
P70 S6k ◽  
Effect Of Glucose

The eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP1) interacts directly with eIF4E and prevents it from forming initiation factor (eIF4F) complexes required for the initiation of cap-dependent mRNA translation. Insulin and other agents induce the phosphorylation of 4E-BP1 at multiple sites, resulting in its release from eIF4E, and this involves signalling through the mammalian target of rapamycin (mTOR). Here we show that d-glucose promotes the ability of insulin to bring about the phosphorylation of 4E-BP1 and the formation of eIF4F complexes. This appears to involve facilitation of the phosphorylation of at least three phosphorylation sites on 4E-BP1, i.e. Thr-36, Thr-45 and Thr-69. Non-metabolizable glucose analogues cannot substitute for d-glucose, but other hexoses can. This suggests that a product of hexose metabolism mediates the permissive effect of glucose. The effect of glucose was concentration-dependent within the range 1–5mM. In contrast with the situation for 4E-BP1, glucose does not allow full activation of the 70kDa ribosomal protein S6 kinase (p70 S6k; another target of mTOR signalling) or phosphorylation, in vivo, of its substrate, ribosomal protein S6. Taken together with earlier data showing that amino acids regulate 4E-BP1 and p70 S6k, the present findings show that 4E-BP1 in particular is regulated in response to the availability of both amino acids and sugars.

scholarly journals Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

2021 ◽  
Vol 23 (1) ◽  
pp. 48
Author(s):  
Yong Weon Yi ◽  
Kyu Sic You ◽  
Jeong-Soo Park ◽  
Seok-Geun Lee ◽  
Yeon-Sun Seong
Keyword(s):  
Ribosomal Protein ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Ribosomal Subunit ◽  
Surrogate Marker ◽  
Mrna Translation ◽  
Ribosomal Protein S6 ◽  
History Of ◽  
Mtorc1 Pathway ◽  
Cancer Types

Ribosomal protein S6 (RPS6) is a component of the 40S small ribosomal subunit and participates in the control of mRNA translation. Additionally, phospho (p)-RPS6 has been recognized as a surrogate marker for the activated PI3K/AKT/mTORC1 pathway, which occurs in many cancer types. However, downstream mechanisms regulated by RPS6 or p-RPS remains elusive, and the therapeutic implication of RPS6 is underappreciated despite an approximately half a century history of research on this protein. In addition, substantial evidence from RPS6 knockdown experiments suggests the potential role of RPS6 in maintaining cancer cell proliferation. This motivates us to investigate the current knowledge of RPS6 functions in cancer. In this review article, we reviewed the current information about the transcriptional regulation, upstream regulators, and extra-ribosomal roles of RPS6, with a focus on its involvement in cancer. We also discussed the therapeutic potential of RPS6 in cancer.

scholarly journals Resistance of Ribosomal Protein mRNA Translation to Protein Synthesis Shutoff Induced by Poliovirus

1999 ◽  
Vol 73 (8) ◽  
pp. 7070-7076 ◽  
Author(s):  
Beatrice Cardinali ◽  
Lucia Fiore ◽  
Nadia Campioni ◽  
Alessandra De Dominicis ◽  
Paola Pierandrei-Amaldi
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Mrna Translation ◽  
Host Protein ◽  
Poliovirus Infection ◽  
Ribosomal Protein S6 ◽  
Cellular Mrnas ◽  
Host Protein Synthesis

ABSTRACT Poliovirus infection induces an overall inhibition of host protein synthesis, although some mRNAs continue to be translated, suggesting different translation requirements for cellular mRNAs. It is known that ribosomal protein mRNAs are translationally regulated and that the phosphorylation of ribosomal protein S6 is involved in the regulation. Here, we report that the translation of ribosomal protein mRNAs resists poliovirus infection and correlates with an increase in p70s6k activity and phosphorylation of ribosomal protein S6.

scholarly journals Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion, Synaptic Plasticity and mRNA Translation

2017 ◽  
Vol 10 ◽  
Author(s):  
Emma Puighermanal ◽  
Anne Biever ◽  
Vincent Pascoli ◽  
Su Melser ◽  
Marine Pratlong ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ribosomal Protein ◽  
Mrna Translation ◽  
Ribosomal Protein S6
Sign in / Sign up

Export Citation Format

Share Document