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.

MP60-12 FOLLICULIN TUMOR SUPPRESSOR BINDS TO TRANSLATION INITIATION FACTORS EIF2G & EIF5B AND SUPPRESSES PROTEIN SYNTHESIS

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Meike Schneider ◽  
Taha Hagar ◽  
Katja Dinkelborg ◽  
Syed I.A. Bukhari ◽  
Axel Haferkamp ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Tumor Suppressor ◽  
Translation Initiation ◽  
Initiation Factors ◽  
Translation Initiation Factors

scholarly journals Near-Cognate Codons Contribute Complexity to Translation Regulation

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
N. Louise Glass
Keyword(s):  
Protein Synthesis ◽  
Cell Fate ◽  
Translation Initiation ◽  
Cellular Response ◽  
Open Reading Frames ◽  
Translation Regulation ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Upstream Open Reading Frames ◽  
Response To Stress

ABSTRACT The interplay between translation initiation, modification of translation initiation factors, and selection of start sites on mRNA for protein synthesis can play a regulatory role in the cellular response to stress, development, and cell fate in eukaryotic species by shaping the proteome. As shown by Ivanov et al. (mBio 8:e00844-17, 2017, https://doi.org/10.1128/mBio.00844-17 !), in the filamentous fungus Neurospora crassa, both upstream open reading frames (uORFs) and near-cognate start codons negatively or positively regulate the translation of the transcription factor CPC1 and production of CPC1 isoforms, which mediate the cellular response to amino acid starvation. Dissecting the physiological roles that differentiate cellular choice of translation initiation is an important parameter to understanding mechanisms that determine cell fate via gene regulation and protein synthesis.

Translation Initiation Factors: Reprogramming Protein Synthesis in Cancer

2016 ◽  
Vol 26 (12) ◽  
pp. 918-933 ◽  
Author(s):  
Jennifer Chu ◽  
Marie Cargnello ◽  
Ivan Topisirovic ◽  
Jerry Pelletier
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Initiation Factors ◽  
Translation Initiation Factors

scholarly journals Composition of Herpesvirus Ribonucleoprotein Complexes

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 119
Author(s):  
Eric S. Pringle ◽  
Craig McCormick
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Viral Protein ◽  
Lytic Replication ◽  
Viral Mrna ◽  
Viral Protein Synthesis ◽  
Initiation Factors ◽  
Ribonucleoprotein Complexes ◽  
Virion Production ◽  
Translation Initiation Factors

Herpesvirus genomes are decoded by host RNA polymerase enzymes, generating messenger ribonucleotides (mRNA) that are post-transcriptionally modified and exported to the cytoplasm through the combined work of host and viral factors. These viral mRNA bear 5′-m7GTP caps and poly(A) tails that should permit the assembly of canonical host eIF4F cap-binding complexes to initiate protein synthesis. However, the precise mechanisms of translation initiation remain to be investigated for Kaposi’s sarcoma-associated herpesvirus (KSHV) and other herpesviruses. During KSHV lytic replication in lymphoid cells, the activation of caspases leads to the cleavage of eIF4G and depletion of eIF4F. Translating mRNPs depleted of eIF4F retain viral mRNA, suggesting that non-eIF4F translation initiation is sufficient to support viral protein synthesis. To identify proteins required to support viral protein synthesis, we isolated and characterized actively translating messenger ribonucleoprotein (mRNP) complexes by ultracentrifugation and sucrose-gradient fractionation followed by quantitative mass spectrometry. The abundance of host translation initiation factors available to initiate viral protein synthesis were comparable between cells undergoing KSHV lytic or latent replication. The translation initiation factors eIF4E2, NCBP1, eIF4G2, and eIF3d were detected in association with actively translating mRNP complexes during KSHV lytic replication, but their depletion by RNA silencing did not affect virion production. By contrast, the N6-methyladenosine methyltransferase METTL3 was required for optimal late gene expression and virion production, but was dispensable for genome replication. Furthermore, we detected several KSHV proteins in actively translating mRNP complexes that had not previously been shown to play roles in viral protein synthesis. We conclude that KSHV usurps distinct host translation initiation systems during latent and lytic phases of infection.

Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs

2003 ◽  
Vol 285 (1) ◽  
pp. E40-E53 ◽  
Author(s):  
Pamela M. J. O'Connor ◽  
Scot R. Kimball ◽  
Agus Suryawan ◽  
Jill A. Bush ◽  
Hanh V. Nguyen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Initiation Factors ◽  
Translation Initiation Factors

Previous studies have shown that intravenous infusion of insulin and/or amino acids reproduces the feeding-induced stimulation of muscle protein synthesis in neonates and that insulin and amino acids act independently to produce this effect. The goal of the present study was to delineate the regulatory roles of insulin and amino acids on muscle protein synthesis in neonates by examining translational control mechanisms, specifically the eukaryotic translation initiation factors (eIFs), which enable coupling of initiator methionyl-tRNAi and mRNA to the 40S ribosomal subunit. Insulin secretion was blocked by somatostatin in fasted 7-day-old pigs ( n = 8–12/group), insulin was infused to achieve plasma levels of ∼0, 2, 6, and 30 μU/ml, and amino acids were clamped at fasting or fed levels or, at the high insulin dose, below fasting. Both insulin and amino acids increased the phosphorylation of ribosomal protein S6 kinase (S6K1) and the eIF4E-binding protein (4E-BP1), decreased the binding of 4E-BP1 to eIF4E, increased eIF4E binding to eIF4G, and increased fractional protein synthesis rates but did not affect eIF2B activity. In the absence of insulin, amino acids had no effect on these translation initiation factors but increased the protein synthesis rates. Raising insulin from below fasting to fasting levels generally did not alter translation initiation factor activity but raised protein synthesis rates. The phosphorylation of S6K1 and 4E-BP1 and the amount of 4E-BP1 bound to eIF4E and eIF4E bound to eIF4G were correlated with insulin level, amino acid level, and protein synthesis rate. Thus insulin and amino acids regulate muscle protein synthesis in skeletal muscle of neonates by modulating the availability of eIF4E for 48S ribosomal complex assembly, although other processes also must be involved.

scholarly journals capCLIP: a new tool to probe protein synthesis in human cells through capture and identification of the eIF4E-mRNA interactome

2020 ◽  
Author(s):  
Kirk B. Jensen ◽  
B. Kate Dredge ◽  
John Toubia ◽  
Xin Jin ◽  
Valentina Iadevaia ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Essential Role ◽  
Human Cells ◽  
Initiation Factors ◽  
Translational Activity ◽  
Translation Initiation Factors ◽  
Eukaryotic Mrnas ◽  
Terminal Oligopyrimidine ◽  
Novel Method

SummaryTranslation of eukaryotic mRNAs starts with binding of the m7G cap to the protein eIF4E followed by recruitment of other translation initiation factors. eIF4E’s essential role in translation suggests the cellular eIF4E-mRNA interactome (or ‘eIF4E cap-ome’) may serve as a faithful proxy of cellular translational activity. Here we describe capCLIP, a novel method to systematically capture and quantify the eIF4E cap-ome. To validate capCLIP, we identified the cap-omes in human cells ± the partial mTORC1 inhibitor rapamycin. As expected, TOP (terminal oligopyrimidine) mRNA representation is systematically reduced in rapamycin-treated cells. capCLIP tag data permits refinement of a 7-nucleotide TOP motif (5′-CUYUYYC-3′). We also apply capCLIP to probe the consequences of phosphorylation of eIF4E, whose function had remained unclear. eIF4E phosphorylation drives an overall reduction in eIF4E-mRNA association; strikingly, mRNAs most sensitive to phosphorylation possess short 5′-UTRs. capCLIP provides a sensitive and comprehensive measure of cellular translational activity. We foresee its application as a high-throughput way to assess translation in contexts not amenable to existing methodologies.

Expression of Translation Initiation Factors eIF-4E and eIF-2α and a Potential Physiologic Role of Continuous Protein Synthesis in Human Platelets

2001 ◽  
Vol 85 (01) ◽  
pp. 142-151 ◽  
Author(s):  
Anping Han ◽  
Linrong Lu ◽  
German Pihan ◽  
Bruce Woda ◽  
Jane-Jane Chen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Ribosomal Subunit ◽  
Human Platelets ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Protein Synthesis Inhibitors ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Rate Limiting

SummaryIt is generally believed that platelets do not have a functionally significant protein synthetic machinery. However, our analysis demonstrated that normal bone marrow megakaryocytes express high levels of translation initiation factors eIF-4E and eIF-2α and the expression of these protein synthesis initiation factors is continued in platelets (as determined by immunohistochemistry and Western blot analysis). Both eIF-4E and eIF-2α are key regulators of protein synthesis. The eIF-4E is a rate-limiting part of a multisubunit complex, eIF-4F, that binds to the 5’ cap structure present in virtually all eukaryotic mRNAs, and carries out transfer of mRNAs to ribosomes for translation. Translation initiation factor eIF-2α is also a rate-limiting protein which associates with two other proteins to form an eIF-2 initiation factor complex responsible for the transfer of initiator methionyl-tRNA to the 40S ribosomal subunit. We confirm that expression of eIF-4E and eIF-2α is biologically relevant in that platelets continue protein synthesis, albeit at a 16 times lower rate than WBC (as determined by 35S-labeled amino acid incorporation, SDS-PAGE and scintillation counting). Finally, we determined that protein synthesis inhibitors (puromycin and emetine) attenuate the platelet aggregation response to a combination of ADP and epinephrine, but potentiate the response to collagen. Our data are consistent with the existence of different signal transducing pathways mediating the response to ADP/epinephrine and collagen. We suggest that the ADP/epinephrine response is positively affected by continuously synthesized proteins, while the response to collagen is modulated by continuously produced inhibitory proteins. Taken together, our results suggest that continuous protein synthesis is important for platelet function and its role in platelet physiology and pathophysiology deserves further study.

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