The mechanism of eukaryotic translation initiation and principles of its regulation

Jackson, Richard J.; Hellen, Christopher U.T.; Pestova, Tatyana V.

doi:10.1038/nrm2838

Cited by 2,358 publications

(2,716 citation statements)

References 118 publications

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“…9 The process of protein translation initiates in almost all human mRNA at AUG codons (corresponding to ATG at the DNA level) resulting in methionine, the primary amino acid in most cellular produced proteins. 10 The initiation site is reached via a ribosome-mediated scanning mechanism. Thus, the ribosome scans in a 5 0 to 3 0 direction until it reaches the AUG nearest to the 5 0 end of the mRNA.…”

Section: Discussionmentioning

confidence: 99%

Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy

et al. 2013

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Isolated metabolic myopathies encompass a heterogeneous group of disorders, with mitochondrial myopathies being a subgroup, with depleted skeletal muscle energy production manifesting either by recurrent episodes of myoglobinuria or progressive muscle weakness. In this study, we investigated the genetic cause of a patient from a consanguineous family who presented with adolescent onset autosomal recessive mitochondrial myopathy. Analysis of enzyme activities of the five respiratory chain complexes in our patients' skeletal muscle showed severely impaired activities of iron sulfur (Fe-S)-dependent complexes I, II and III and mitochondrial aconitase. We employed exome sequencing combined with homozygosity mapping to identify a homozygous mutation, c.1A4T, in the FDX1L gene, which encodes the mitochondrial ferredoxin 2 (Fdx2) protein. The mutation disrupts the ATG initiation translation site resulting in severe reduction of Fdx2 content in the patient muscle and fibroblasts mitochondria. Fdx2 is the second component of the Fe-S cluster biogenesis machinery, the first being IscU that is associated with isolated mitochondrial myopathy. We suggest adding genetic analysis of FDX1L in cases of mitochondrial myopathy especially when associated with reduced activity of the respiratory chain complexes I, II and III.

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Section: Discussionmentioning

confidence: 99%

Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy

et al. 2013

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“…Loss of translation control may lead to cell malignant transformation as consequence of increased rate of protein synthesis and translation activation of mRNA species that are relevant for cell proliferation and survival. Initiation of protein synthesis of most eukaryotic mRNAs is m 7 G-cap-dependent and requires at least 13 eukaryotic initiation factors (eIFs) [16]. Interleukin-1 receptor associated kinases (IRAKs), were originally described as transducers for inducing various inflammatory cytokines and later implicated as critical mediators in regulation of TLR/IL-1R signaling [8].…”

Section: Resultsmentioning

confidence: 99%

Differential proteomic analysis of respiratory samples from patients suffering from influenza

et al. 2016

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The exact molecular pathways involved in the pathogenesis of influenza are yet unclear. In the present study we investigated the upper respiratory proteome in influenza patients. 200 nasal and throat swab samples were collected from patients suffering from acute respiratory illness. These samples were confirmed for influenza pandemic A/H1N1/2009 and influenza type B using qRT-PCR. 10 similar swabs were collected from healthy individuals and were used as controls. Proteins were extracted from the cell pellets and were subjected to 2-D gel electrophoresis. The differentially expressed proteins were identified using MALDI-TOF. Identified proteins were classified into different functional groups based on functions reported in the databases. 25 % of these proteins were involved in cytoskeletal formation, whereas 14 % were involved in signal transduction. Proteins involved in anti-viral responses, Ca-signaling, transport, and tumor suppression constituted 10 % each, where as 5 % of proteins each belong to Nicotinic acetylcholine receptor, Protein Synthesis and anti-bacterial proteins. 10 % of the proteins have not been described previously. This is the first report on respiratory proteome profile in Influenza patients. The study emphasizes the role of such profiling studies using multiple platforms for bio-marker discoveries, especially non-invasive diagnostic marker in Influenza and other infectious diseases.

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“…The terminal 5′ 7-methylguanosine cap and 3′ poly(A) tail modifications found on mature mRNAs serve to both promote transcript association with the translation machinery and protect transcripts from exonuclease-mediated decay [22], and their enzymatic removal inhibits translation and destabilizes mRNAs. As the first and rate limiting step in mRNA decay, deadenylation is therefore an important regulatory nexus.…”

Section: Post-transcriptional Control Of Mrna Abundance and Stabilitymentioning

confidence: 99%

Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries

2018

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Post-transcriptional control of messenger RNA (mRNA) is an important layer of gene regulation that modulates mRNA decay, translation, and localization. Eukaryotic mRNA decay begins with the catalytic removal of the 3′ poly-adenosine tail by deadenylase enzymes. Multiple deadenylases have been identified in vertebrates and are known to have distinct biological roles; among these proteins is Nocturnin, which has been linked to circadian biology, adipogenesis, osteogenesis, and obesity. Multiple studies have investigated Nocturnin’s involvement in these processes; however, a full understanding of its molecular function remains elusive. Recent studies have provided new insights by identifying putative Nocturnin-regulated mRNAs in mice and by determining the structure and regulatory activities of human Nocturnin. This review seeks to integrate these new discoveries into our understanding of Nocturnin’s regulatory functions and highlight the important remaining unanswered questions surrounding its regulation, biochemical activities, protein partners, and target mRNAs.

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The mechanism of eukaryotic translation initiation and principles of its regulation

Cited by 2,358 publications

References 118 publications

Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy

Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy

Differential proteomic analysis of respiratory samples from patients suffering from influenza

Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries

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