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Limited By:	Author = Atkins, John F.;

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Displaying Results 26 - 31 of 31 on page 2 of 2

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Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform (2016)

Tzani, Ioanna; Ivanov, Ivaylo P.; Andreev, Dmitry E.; Dmitriev, Ruslan I.; Dean, Kellie...

Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform (2016)

Tzani, Ioanna; Ivanov, Ivaylo P.; Andreev, Dmitry E.; Dmitriev, Ruslan I.; Dean, Kellie A.; Baranov, Pavel V.; Atkins, John F.; Loughran, Gary

Abstract:

Abundant evidence for translation within the 5′ leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5′ leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5′ leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5′ leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-term...

http://hdl.handle.net/10468/5715

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Transcriptional frameshifting rescues Citrobacter rodentium Type VI secretion by the production of two length variants from the prematurely interrupted tssM gene (2014)

Gueguen, Erwan; Wills, Norma M.; Atkins, John F.; Cascales, Eric

Transcriptional frameshifting rescues Citrobacter rodentium Type VI secretion by the production of two length variants from the prematurely interrupted tssM gene (2014)

Gueguen, Erwan; Wills, Norma M.; Atkins, John F.; Cascales, Eric

Abstract:

The Type VI secretion system (T6SS) mediates toxin delivery into both eukaryotic and prokaryotic cells. It is composed of a cytoplasmic structure resembling the tail of contractile bacteriophages anchored to the cell envelope through a membrane complex composed of the TssL and TssM inner membrane proteins and of the TssJ outer membrane lipoprotein. The C-terminal domain of TssM is required for its interaction with TssJ, and for the function of the T6SS. In Citrobacter rodentium, the tssM1 gene does not encode the C-terminal domain. However, the stop codon is preceded by a run of 11 consecutive adenosines. In this study, we demonstrate that this poly-A tract is a transcriptional slippery site that induces the incorporation of additional adenosines, leading to frameshifting, and hence the production of two TssM1 variants, including a full-length canonical protein. We show that both forms of TssM1, and the ratio between these two forms, are required for the function of the T6SS in C. r...

http://hdl.handle.net/10468/2319

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Transcriptional slippage in the positive-sense RNA virus family Potyviridae (2015)

Olspert, Allan; Chung, Betty Y-W; Atkins, John F.; Carr, John P.; Firth, Andrew E.

Transcriptional slippage in the positive-sense RNA virus family Potyviridae (2015)

Olspert, Allan; Chung, Betty Y-W; Atkins, John F.; Carr, John P.; Firth, Andrew E.

Abstract:

The family Potyviridae encompasses ~30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N‐PIPO, which is essential for virus cell‐to‐cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N‐PIPO. The slippage efficiency is ~2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative‐sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene exp...

http://hdl.handle.net/10468/5718

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Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity (2017)

Ivanov, Ivaylo P.; Wei, Jiajie; Caster, Stephen Z.; Smith, Kristina M.; Michel, Audrey ...

Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity (2017)

Ivanov, Ivaylo P.; Wei, Jiajie; Caster, Stephen Z.; Smith, Kristina M.; Michel, Audrey M.; Zhang, Ying; Firth, Andrew E.; Freitag, Michael; Dunlap, Jay C.; Bell-Pedersen, Deborah; Atkins, John F.; Sachs, Matthew S.

Abstract:

Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5' region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5' conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs) in the CPC1 reading frame upstream of uORF2, some deeply conserved, could...

http://hdl.handle.net/10468/4788

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Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection (2018)

Loughran, Gary; Firth, Andrew E.; Atkins, John F.; Ivanov, Ivaylo P.

Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection (2018)

Loughran, Gary; Firth, Andrew E.; Atkins, John F.; Ivanov, Ivaylo P.

Abstract:

The efficiency of start codon selection during ribosomal scanning in eukaryotic translation initiation is influenced by the context or flanking nucleotides surrounding the AUG codon. The levels of eukaryotic translation initiation factors 1 (eIF1) and 5 (eIF5) play critical roles in controlling the stringency of translation start site selection. The basic leucine zipper and W2 domain-containing proteins 1 and 2 (BZW1 and BZW2), also known as eIF5-mimic proteins, are paralogous human proteins containing C-terminal HEAT domains that resemble the HEAT domain of eIF5. We show that translation of mRNAs encoding BZW1 and BZW2 homologs in fungi, plants and metazoans is initiated by AUG codons in conserved unfavorable initiation contexts. This conservation is reminiscent of the conserved unfavorable initiation context that enables autoregulation of EIF1. We show that overexpression of BZW1 and BZW2 proteins enhances the stringency of start site selection, and that their poor initiation codo...

http://hdl.handle.net/10468/5719

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Two groups of phenylalanine biosynthetic operon leader peptides genes: a high level of apparently incidental frameshifting in decoding Escherichia coli pheL (2011)

Gurvich, Olga L.; Näsvall, S. Joakim; Baranov, Pavel V.; Björk, Glenn R.; Atkins, John F.

Two groups of phenylalanine biosynthetic operon leader peptides genes: a high level of apparently incidental frameshifting in decoding Escherichia coli pheL (2011)

Gurvich, Olga L.; Näsvall, S. Joakim; Baranov, Pavel V.; Björk, Glenn R.; Atkins, John F.

Abstract:

The bacterial pheL gene encodes the leader peptide for the phenylalanine biosynthetic operon. Translation of pheL mRNA controls transcription attenuation and, consequently, expression of the downstream pheA gene. Fifty-three unique pheL genes have been identified in sequenced genomes of the gamma subdivision. There are two groups of pheL genes, both of which are short and contain a run(s) of phenylalanine codons at an inteRNAl position. One group is somewhat diverse and features different termination and 5'-flanking codons. The other group, mostly restricted to Enterobacteria and including Escherichia coli pheL, has a conserved nucleotide sequence that ends with UUC_CCC_UGA. When these three codons in E. coli pheL mRNA are in the ribosomal E-, P- and A-sites, there is an unusually high level, 15%, of +1 ribosomal frameshifting due to features of the nascent peptide sequence that include the penultimate phenylalanine. This level increases to 60% with a natural, heterologous, nas...

http://hdl.handle.net/10468/5025

Displaying Results 26 - 31 of 31 on page 2 of 2