scholarly journals Codon usage and amino acid identity are major determinants of mRNA stability in humans

2018 ◽  
Author(s):  
Megan E. Forrest ◽  
Ashrut Narula ◽  
Thomas J Sweet ◽  
Daniel Arango ◽  
Gavin Hanson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Codon Usage ◽  
Mrna Stability ◽  
Protein Sequence ◽  
Synonymous Codon ◽  
Amino Acid Identity ◽  
Mrna Degradation ◽  
Model Organisms ◽  
Mrna Levels ◽  
Acid Identity

mRNA degradation is a critical, yet poorly understood, aspect of gene expression. Previous studies demonstrate that codon content acts as a major determinant of mRNA stability in model organisms. In humans, the importance of open reading frame (ORF)-mediated regulation remains unclear. Here, we globally analyzed mRNA stability for both endogenous and human ORFeome collection mRNAs in human cells. Consistent with previous studies, we observed that synonymous codon usage impacts human mRNA decay. Unexpectedly, amino acid identity also acts as a driver of translation-dependent decay, meaning that primary protein sequence dictates overall mRNA levels and, consequently, protein abundance. Both codon usage and amino acid identity affect translational elongation rate to varying degrees in distinct organisms, with the net result being sensed by mRNA degradation machinery. In humans, interplay between ORF- and UTR-mediated control of mRNA stability may be critical to offset this fundamental relationship between protein sequence and mRNA abundance.

scholarly journals Codon Usage and Amino Acid Identity Are Major Determinants of MRNA Stability in Humans

2018 ◽  
Author(s):  
Megan E. Forrest ◽  
Ashrut Narula ◽  
Thomas J. Sweet ◽  
Daniel Arango ◽  
Gavin Hanson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Codon Usage ◽  
Mrna Stability ◽  
Amino Acid Identity ◽  
Acid Identity

Differential regulation of trypsinogen mRNA translation: full-length mRNA sequences encoding two oppositely charged trypsinogen isoenzymes in the dog pancreas

1985 ◽  
Vol 5 (10) ◽  
pp. 2669-2676
Author(s):  
S D Pinsky ◽  
K S LaForge ◽  
G Scheele
Keyword(s):  
Amino Acid ◽  
Mrna Translation ◽  
Amino Acid Identity ◽  
Full Length ◽  
In Vitro Translation ◽  
Mrna Levels ◽  
Acid Identity ◽  
Noncoding Regions ◽  
Amino Terminal ◽  
Cationic Trypsinogen

In the absence of changes in functional mRNA levels, stimulation of the pancreas with caerulein, a peptide analog of cholecystokinin, has been previously shown to increase the synthesis of anionic but not cationic trypsinogen. To look for structure-function correlations, a high-yield, full-length cDNA library has been constructed from canine pancreatic poly(A)+ mRNA. Full-length clones coding for the two major trypsinogen isoenzyme forms have been identified by colony hybridization and verified by in vitro translation of hybrid-selected mRNA in the presence of microsomal membranes and an optimal redox potential. Disulfide-bonded translation products were separated and identified by two-dimensional isoelectric focusing-sodium dodecyl sulfate-gel electrophoresis. Nucleotide sequence analysis allowed us to deduce the amino acid sequences for the anionic and cationic forms of canine trypsinogen, which contain 232 and 231 residues, respectively (77% amino acid identity), and the 15-residue amino terminal signal sequences (53% amino acid identity) associated with the two presecretory forms. Measurements of relative and absolute mRNA levels, when related to relative protein synthesis values, indicated that the translational efficiency of anionic trypsinogen mRNA exceeded that of cationic trypsinogen mRNA by 1.5- to 2.9-fold under basal conditions. Analysis of the 5' noncoding regions of trypsinogen mRNAs revealed a striking conservation of sequence (10 of 12 bases) between dog and rat anionic trypsinogen forms. This contrasted markedly with the divergence of the 5' noncoding regions observed between dog anionic and cationic trypsinogen mRNAs.

scholarly journals Differential regulation of trypsinogen mRNA translation: full-length mRNA sequences encoding two oppositely charged trypsinogen isoenzymes in the dog pancreas.

1985 ◽  
Vol 5 (10) ◽  
pp. 2669-2676 ◽  
Author(s):  
S D Pinsky ◽  
K S LaForge ◽  
G Scheele
Keyword(s):  
Amino Acid ◽  
Mrna Translation ◽  
Amino Acid Identity ◽  
Full Length ◽  
In Vitro Translation ◽  
Mrna Levels ◽  
Acid Identity ◽  
Noncoding Regions ◽  
Amino Terminal ◽  
Cationic Trypsinogen

In the absence of changes in functional mRNA levels, stimulation of the pancreas with caerulein, a peptide analog of cholecystokinin, has been previously shown to increase the synthesis of anionic but not cationic trypsinogen. To look for structure-function correlations, a high-yield, full-length cDNA library has been constructed from canine pancreatic poly(A)+ mRNA. Full-length clones coding for the two major trypsinogen isoenzyme forms have been identified by colony hybridization and verified by in vitro translation of hybrid-selected mRNA in the presence of microsomal membranes and an optimal redox potential. Disulfide-bonded translation products were separated and identified by two-dimensional isoelectric focusing-sodium dodecyl sulfate-gel electrophoresis. Nucleotide sequence analysis allowed us to deduce the amino acid sequences for the anionic and cationic forms of canine trypsinogen, which contain 232 and 231 residues, respectively (77% amino acid identity), and the 15-residue amino terminal signal sequences (53% amino acid identity) associated with the two presecretory forms. Measurements of relative and absolute mRNA levels, when related to relative protein synthesis values, indicated that the translational efficiency of anionic trypsinogen mRNA exceeded that of cationic trypsinogen mRNA by 1.5- to 2.9-fold under basal conditions. Analysis of the 5' noncoding regions of trypsinogen mRNAs revealed a striking conservation of sequence (10 of 12 bases) between dog and rat anionic trypsinogen forms. This contrasted markedly with the divergence of the 5' noncoding regions observed between dog anionic and cationic trypsinogen mRNAs.

scholarly journals Translation elongation and mRNA stability are coupled through the ribosomal A-site

2018 ◽  
Author(s):  
Gavin Hanson ◽  
Najwa Alhusaini ◽  
Nathan Morris ◽  
Thomas Sweet ◽  
Jeff Coller
Keyword(s):  
Amino Acid ◽  
Mrna Stability ◽  
Transcript Level ◽  
Amino Acid Identity ◽  
Elongation Rate ◽  
Ribosome Profiling ◽  
Translation Elongation ◽  
Acid Identity ◽  
Optimal Codons ◽  
A Site

AbstractMessenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increase mRNA stability. However, a direct link between elongation rate and mRNA stability has not been established across the entire yeast transcriptome. In addition, there is evidence from work in higher eukaryotes that amino acid identity influences mRNA stability, raising the question as to whether the impact of translation elongation on mRNA decay is at the level of tRNA decoding, amino acid incorporation, or some combination of each. To address these questions, we performed ribosome profiling of wildtype yeast. In good agreement with other studies, our data showed faster codon-specific elongation over optimal codons and faster transcript-level elongation correlating with transcript optimality. At both the codon-level and transcript-level, faster elongation correlated with increased mRNA stability. These findings were reinforced by showing increased translation efficiency and kinetics for a panel of 11 HIS3 reporter mRNAs of increasing codon optimality. While we did observe that elongation measured by ribosome profiling is composed of both amino acid identity and synonymous codon effects, further analyses of these data establish that A-site tRNA decoding rather than other steps of translation elongation is driving mRNA decay in yeast.

DLH1 is a Functional Candida albicans Homologue of the Meiosis-Specific Gene DMC1

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 769-776 ◽  
Author(s):  
Andrew C Diener ◽  
Gerald R Fink
Keyword(s):  
Escherichia Coli ◽  
Candida Albicans ◽  
Amino Acid ◽  
Meiotic Recombination ◽  
Protein Sequence ◽  
Amino Acid Identity ◽  
Specific Gene ◽  
Null Mutant ◽  
Acid Identity

Abstract DMC1/LIM15 homologue 1 (DLH1), a gene related to meiosis-specific genes, has been isolated from Candida albicans, a fungus thought not to undergo meiosis. The deduced protein sequence of DLH1 contains 74% amino acid identity with Dmclp from Saccharomyces cermisiae and 63% with Liml5p from the plant Lilium long)lmm, meiosisspecific homologues of Escherichia coli RecA. Candida DLH1 complements a dmcl/dmcl null mutant in S. cermisiae: High copy expression of DLH1 restores both sporulation and meiotic recombination to a Saccharomyces dmclΔ/dmclΔ strain. Unlike the DMCl gene, which is transcribed only in meiotic cells, the heterologous Candida DLH1 gene is transcribed in both vegetative and meiotic cells of S. cermisiae. Transcription of DLH1 is not detected or induced in C. albicans under conditions that induce DMC1 and meiosis in S. cermisiae. The presence of an intact homologue of a meiosis-specific gene in C. albicans raises the possibility that this organism has a cryptic meiotic pathway.

scholarly journals A50 Whole-genome sequencing of African swine fever isolates from Sardinia

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
C Torresi ◽  
F Granberg ◽  
L Bertolotti ◽  
A Oggiano ◽  
B Colitti ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sequence Data ◽  
Temporal Distribution ◽  
African Swine Fever ◽  
Amino Acid Identity ◽  
Genotype I ◽  
Acid Identity ◽  
Wide Range ◽  
Intergenic Sequences ◽  
Genes Encoding

Abstract In order to assess the molecular epidemiology of African swine fever (ASF) in Sardinia, we analyzed a wide range of isolates from wild and domestic pigs over a 31-year period (1978–2009) by genotyping sequence data from the genes encoding the p54 and the p72 proteins and the CVR. On this basis, the analysis of the B602L gene revealed a minor difference, placing the Sardinian isolates into two clusters according to their temporal distribution. As an extension of this study, in order to achieve a higher level of discrimination, three further variable genome regions, namely p30, CD2v, and I73R/I329L, of a large number of isolates collected from outbreaks in the years 2002–14 have been investigated. Sequence analysis of the CD2v region revealed a temporal subdivision of the viruses into two subgroups. These data, together with those from the B602L gene analysis, demonstrated that the viruses circulating in Sardinia belong to p72/genotype I, but since 1990 have undergone minor genetic variations in respect to its ancestor, thus making it impossible to trace isolates, enabling a more accurate assessment of the origin of outbreaks, and extending knowledge of virus evolution. To solve this problem, we have sequenced and annotated the complete genome of nine ASF isolates collected in Sardinia between 1978 and 2012. This was achieved using sequence data determined by next-generation sequencing. The results showed a very high identity with range of nucleotide similarity among isolates of 99.5 per cent to 99.9 per cent. The ASF virus (ASFV) genomes were composed of terminal inverted repeats and conserved and non-conserved ORFs. Among the conserved ORFs, B385R, H339R, and O61R-p12 showed 100 per cent amino acid identity. The same was true for the hypervariable ORFs, with regard to X69R, DP96R, DP60R, EP153R, B407L, I10L, and L60L genes. The EP402R and B602L genes showed, as expected, an amino acid identity range of 98.5 per cent to 100 per cent and 91 per cent to 100 per cent, respectively. In addition, all of the isolates displayed variable intergenic sequences. As a whole, the results from our studies confirmed a remarkable genetic stability of the ASFV/p72 genotype I viruses circulating in Sardinia.

Characterization and Induction of Two Cytochrome P450 Genes, CYP6AE28 and CYP6AE30, in Cnaphalocrocis medinalis: Possible Involvement in Metabolism of Rice Allelochemicals

2010 ◽  
Vol 65 (11-12) ◽  
pp. 719-725 ◽  
Author(s):  
Xiaoli Liu ◽  
Jun Chen ◽  
Zhifan Yang
Keyword(s):  
Amino Acid ◽  
Rice Variety ◽  
Amino Acid Identity ◽  
Cnaphalocrocis Medinalis ◽  
Amino Acid Residues ◽  
Acid Identity ◽  
Rice Leaf Folder ◽  
Cytochrome P450 Genes ◽  
Molecular Masses ◽  
Lepidoptera Pyralidae

Two cDNAs specific for P450 genes, CYP6AE28 and CYP6AE30, have been isolated from the rice leaf folder Cnaphalocrocis medinalis Guenée (Lepidoptera: Pyralidae). Both cDNApredicted proteins have 504 amino acid residues in length, but with molecular masses of 60177 Dalton for CYP6AE28 and 60020 Dalton for CYP6AE30, and theoretical pI values of 8.49 for CYP6AE28 and 8.56 for CYP6AE30, respectively. Both putative proteins contain the conserved structural and functional domains characteristic of all CYP6 members. CYP6AE28 and CYP6AE30 show 52% amino acid identity to each other; both of them have 49 - 56% identities with CYP6AE1, Cyp6ae12, and CYP6AE14. Phylogenetic analysis showed that the two P450s are grouped in the lineage containing some of the CYP6AE members, CYP6B P450s and CYP321A1. The transcripts of CYP6AE28 and CYP6AE30 were found to be induced in response to TKM-6, a rice variety with high resistance to C. medinalis. The results suggest that the two P450s may play important roles in adaptation to the host plant rice. This is the first report of P450 genes cloned in C. medinalis

scholarly journals PFM-Like Enzymes Are a Novel Family of Subclass B2 Metallo-β-Lactamases from Pseudomonas synxantha Belonging to the Pseudomonas fluorescens Complex

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Laurent Poirel ◽  
Mattia Palmieri ◽  
Michael Brilhante ◽  
Amandine Masseron ◽  
Vincent Perreten ◽  
...  
Keyword(s):  
Amino Acid ◽  
Pseudomonas Fluorescens ◽  
Bacterial Species ◽  
Amino Acid Identity ◽  
Chicken Meat ◽  
The Novel ◽  
Content Type ◽  
Acid Identity ◽  
Carbapenem Resistant ◽  
Encoding Genes

ABSTRACT A carbapenem-resistant Pseudomonas synxantha isolate recovered from chicken meat produced the novel carbapenemase PFM-1. That subclass B2 metallo-β-lactamase shared 71% amino acid identity with β-lactamase Sfh-1 from Serratia fonticola. The blaPFM-1 gene was chromosomally located and likely acquired. Variants of PFM-1 sharing 90% to 92% amino acid identity were identified in bacterial species belonging to the Pseudomonas fluorescens complex, including Pseudomonas libanensis (PFM-2) and Pseudomonas fluorescens (PFM-3), highlighting that these species constitute reservoirs of PFM-like encoding genes.

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