scholarly journals Eukaryote-specific Domains in Translation Initiation Factors: Implications for Translation Regulation and Evolution of the Translation System

2000 ◽  
Vol 10 (8) ◽  
pp. 1172-1184 ◽  
Author(s):  
L. Aravind
Keyword(s):  
Translation Initiation ◽  
Translation Regulation ◽  
Translation System ◽  
Initiation Factors ◽  
Translation Initiation Factors

scholarly journals eIF4G-driven translation initiation of downstream ORFs in mammalian cells

2020 ◽  
Vol 48 (18) ◽  
pp. 10441-10455
Author(s):  
Risa Nobuta ◽  
Kodai Machida ◽  
Misaki Sato ◽  
Satoshi Hashimoto ◽  
Yasuhito Toriumi ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Mammalian Cells ◽  
Open Reading Frames ◽  
Translation System ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Genome Wide

Abstract Comprehensive genome-wide analysis has revealed the presence of translational elements in the 3′ untranslated regions (UTRs) of human transcripts. However, the mechanisms by which translation is initiated in 3′ UTRs and the physiological function of their products remain unclear. This study showed that eIF4G drives the translation of various downstream open reading frames (dORFs) in 3′ UTRs. The 3′ UTR of GCH1, which encodes GTP cyclohydrolase 1, contains an internal ribosome entry site (IRES) that initiates the translation of dORFs. An in vitro reconstituted translation system showed that the IRES in the 3′ UTR of GCH1 required eIF4G and conventional translation initiation factors, except eIF4E, for AUG-initiated translation of dORFs. The 3′ UTR of GCH1-mediated translation was resistant to the mTOR inhibitor Torin 1, which inhibits cap-dependent initiation by increasing eIF4E-unbound eIF4G. eIF4G was also required for the activity of various elements, including polyU and poliovirus type 2, a short element thought to recruit ribosomes by base-pairing with 18S rRNA. These findings indicate that eIF4G mediates translation initiation of various ORFs in mammalian cells, suggesting that the 3′ UTRs of mRNAs may encode various products.

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.

scholarly journals eIF5B gates the transition from translation initiation to elongation

2019 ◽  
Author(s):  
Jinfan Wang ◽  
Alex G. Johnson ◽  
Christopher P. Lapointe ◽  
Junhong Choi ◽  
Arjun Prabhakar ◽  
...  
Keyword(s):  
Single Molecule ◽  
Translation Initiation ◽  
Protein Product ◽  
Initiation Factor ◽  
Translation System ◽  
80S Ribosome ◽  
Reading Frame ◽  
Initiation Factors ◽  
Translation Initiation Factors

Translation initiation determines both the quantity and identity of the protein product by establishing the reading frame for protein synthesis. In eukaryotic cells, numerous translation initiation factors (eIFs) prepare ribosomes for polypeptide elongation, yet the underlying dynamics of this process remain enigmatic1–4. A central question is how eukaryotic ribosomes transition from translation initiation to elongation. Here, we applied in vitro single-molecule fluorescence microscopy approaches to monitor directly in real time the pathways of late translation initiation and the transition to elongation using a purified yeast Saccharomyces cerevisiae translation system. This transition was remarkably slower in our eukaryotic system than that reported for Escherichia coli5–7. The slow entry to elongation was defined by a long residence time of eIF5B on the 80S ribosome after joining of individual ribosomal subunits, which is catalyzed by this universally conserved initiation factor. Inhibition of eIF5B GTPase activity following subunit joining prevented eIF5B dissociation from the 80S complex, thereby preventing elongation. Our findings illustrate how eIF5B dissociation serves as a kinetic checkpoint for the transition from initiation to elongation, and its release may be governed by a conformation of the ribosome complex that triggers GTP hydrolysis.

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.

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