scholarly journals Accumulation of Polyadenylated mRNA, Pab1p, eIF4E, and eIF4G with P-Bodies inSaccharomyces cerevisiae

2007 ◽  
Vol 18 (7) ◽  
pp. 2592-2602 ◽  
Author(s):  
Muriel Brengues ◽  
Roy Parker
Keyword(s):  
Transition State ◽  
Stationary Phase ◽  
Translation Initiation ◽  
Glucose Deprivation ◽  
Mrna Decapping ◽  
P Bodies ◽  
Low Level ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Polyadenylated Mrna

Recent experiments have shown that mRNAs can move between polysomes and P-bodies, which are aggregates of nontranslating mRNAs associated with translational repressors and the mRNA decapping machinery. The transitions between polysomes and P-bodies and how the poly(A) tail and the associated poly(A) binding protein 1 (Pab1p) may affect this process are unknown. Herein, we provide evidence that poly(A)+mRNAs can enter P-bodies in yeast. First, we show that both poly(A)−and poly(A)+mRNA become translationally repressed during glucose deprivation, where mRNAs accumulate in P-bodies. In addition, both poly(A)+transcripts and/or Pab1p can be detected in P-bodies during glucose deprivation and in stationary phase. Cells lacking Pab1p have enlarged P-bodies, suggesting that Pab1p plays a direct or indirect role in shifting the equilibrium of mRNAs away from P-bodies and into translation, perhaps by aiding in the assembly of a type of mRNP within P-bodies that is poised to reenter translation. Consistent with this latter possibility, we observed the translation initiation factors (eIF)4E and eIF4G in P-bodies at a low level during glucose deprivation and at high levels in stationary phase. Moreover, Pab1p exited P-bodies much faster than Dcp2p when stationary phase cells were given fresh nutrients. Together, these results suggest that polyadenylated mRNAs can enter P-bodies, and an mRNP complex including poly(A)+mRNA, Pab1p, eIF4E, and eIF4G2 may represent a transition state during the process of mRNAs exchanging between P-bodies and translation.

scholarly journals Mammalian stress granules and P bodies at a glance

2020 ◽  
Vol 133 (16) ◽  
pp. jcs242487 ◽  
Author(s):  
Claire L. Riggs ◽  
Nancy Kedersha ◽  
Pavel Ivanov ◽  
Paul Anderson
Keyword(s):  
Translation Initiation ◽  
Stress Granules ◽  
Detailed Knowledge ◽  
Processing Bodies ◽  
P Bodies ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Response To Stress ◽  
Cellular Compartments ◽  
Liquid Liquid Phase Separation

ABSTRACTStress granules (SGs) and processing bodies (PBs) are membraneless ribonucleoprotein-based cellular compartments that assemble in response to stress. SGs and PBs form through liquid–liquid phase separation that is driven by high local concentrations of key proteins and RNAs, both of which dynamically shuttle between the granules and the cytoplasm. SGs uniquely contain certain translation initiation factors and PBs are uniquely enriched with factors related to mRNA degradation and decay, although recent analyses reveal much broader protein commonality between these granules. Despite detailed knowledge of their composition and dynamics, the function of SGs and PBs remains poorly understood. Both, however, contain mRNAs, implicating their assembly in the regulation of RNA metabolism. SGs may also serve as hubs that rewire signaling events during stress. By contrast, PBs may constitute RNA storage centers, independent of mRNA decay. The aberrant assembly or disassembly of these granules has pathological implications in cancer, viral infection and neurodegeneration. Here, we review the current concepts regarding the formation, composition, dynamics, function and involvement in disease of SGs and PBs.

Subcellular localization of mRNA and factors involved in translation initiation

2008 ◽  
Vol 36 (4) ◽  
pp. 648-652 ◽  
Author(s):  
Nathaniel P. Hoyle ◽  
Mark P. Ashe
Keyword(s):  
Protein Synthesis ◽  
Subcellular Localization ◽  
Translation Initiation ◽  
Potential Functions ◽  
Present Review ◽  
Cellular Activity ◽  
Initiation Factors ◽  
Translation Initiation Factors

Both the process and synthesis of factors required for protein synthesis (or translation) account for a large proportion of cellular activity. In eukaryotes, the most complex and highly regulated phase of protein synthesis is that of initiation. For instance, across eukaryotes, at least 12 factors containing 22 or more proteins are involved, and there are several regulated steps. Recently, the localization of mRNA and factors involved in translation has received increased attention. The present review provides a general background to the subcellular localization of mRNA and translation initiation factors, and focuses on the potential functions of localized translation initiation factors. That is, as genuine sites for translation initiation, as repositories for factors and mRNA, and as sites of regulation.

scholarly journals Leaderless mRNAs Bind 70S Ribosomes More Strongly than 30S Ribosomal Subunits in Escherichia coli

2002 ◽  
Vol 184 (23) ◽  
pp. 6730-6733 ◽  
Author(s):  
Sean M. O'Donnell ◽  
Gary R. Janssen
Keyword(s):  
Escherichia Coli ◽  
Translation Initiation ◽  
Primer Extension ◽  
Ribosomal Subunits ◽  
Ribosome Binding ◽  
Initiation Factors ◽  
Translation Initiation Factors

ABSTRACT By primer extension inhibition assays, 70S ribosomes bound with higher affinity, or stability, than did 30S subunits to leaderless mRNAs containing AUG or GUG start codons. Addition of translation initiation factors affected ribosome binding to leaderless mRNAs. Our results suggest that translation of leaderless mRNAs might initiate through a pathway involving 70S ribosomes or 30S subunits lacking IF3.

scholarly journals Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation

2021 ◽  
Vol 118 (6) ◽  
pp. e2017715118
Author(s):  
Christopher P. Lapointe ◽  
Rosslyn Grosely ◽  
Alex G. Johnson ◽  
Jinfan Wang ◽  
Israel S. Fernández ◽  
...  
Keyword(s):  
Single Molecule ◽  
Translation Initiation ◽  
Ribosomal Subunit ◽  
Start Codon ◽  
Messenger Rnas ◽  
Eukaryotic Translation ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
40S Ribosomal Subunit ◽  
Eukaryotic Translation Initiation Factors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-CoV that recently emerged as a human pathogen and is the causative agent of the COVID-19 pandemic. A molecular framework of how the virus manipulates host cellular machinery to facilitate infection remains unclear. Here, we focus on SARS-CoV-2 NSP1, which is proposed to be a virulence factor that inhibits protein synthesis by directly binding the human ribosome. We demonstrate biochemically that NSP1 inhibits translation of model human and SARS-CoV-2 messenger RNAs (mRNAs). NSP1 specifically binds to the small (40S) ribosomal subunit, which is required for translation inhibition. Using single-molecule fluorescence assays to monitor NSP1–40S subunit binding in real time, we determine that eukaryotic translation initiation factors (eIFs) allosterically modulate the interaction of NSP1 with ribosomal preinitiation complexes in the absence of mRNA. We further elucidate that NSP1 competes with RNA segments downstream of the start codon to bind the 40S subunit and that the protein is unable to associate rapidly with 80S ribosomes assembled on an mRNA. Collectively, our findings support a model where NSP1 proteins from viruses in at least two subgenera of beta-CoVs associate with the open head conformation of the 40S subunit to inhibit an early step of translation, by preventing accommodation of mRNA within the entry channel.

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