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PubMed2026

Photocatalytic Golgi Proteomics Reveals Palmitoylation-Regulated Golgiphagy.

The Golgi apparatus (GA) orchestrates protein modification, trafficking, and secretion through highly dynamic remodeling, yet its proteomic complexity remains difficult to resolve in living systems. Here, we report CAT-Golgi, a genetically independent and light-controlled photocatalytic proximity labeling strategy for in situ spatiotemporal mapping of the Golgi-associated proteome. Combining a cysteine-conjugated eosin photocatalyst (GolgiCat) with an aniline probe, CAT-Golgi enables rapid and precise protein labeling within minutes under mild green light, requiring no genetic manipulation and operating efficiently in hard-to-transfect and primary cells. Leveraging our extensive efforts in organelle-targeted photocatalytic systems, we extended this chemistry to the highly dynamic and reversible Golgi apparatus. CAT-Golgi achieved quantitative and comparative proteomics in HeLa, K562, Jurkat and primary HEKa cells, revealing both conserved and cell-type-specific profiles. Under Brefeldin A-induced Golgiphagy, CAT-Golgi captured large-scale proteome remodeling and identified palmitoyl-protein thioesterase 1 (PPT1) as a potential regulatory component. PPT1 downregulation enhanced ULK1 and TRPML1 palmitoylation, disrupted redox balance, and activated Golgiphagy. CAT-Golgi provides a broadly applicable chemical platform for decoding organelle dynamics, offering both conceptual and technical foundations for extending photocatalytic proteomics to other transient organelles and illuminating molecular mechanisms of organelle plasticity and disease progression.

Golgi Apparatus↗
PubMed2006

Identification and characterization of a +1 frameshift observed during the expression of Epstein-Barr virus IL-10 in Escherichia coli.

Epstein-Barr virus IL-10 (ebvIL-10) mimics the biological functions of cellular IL-10 including a number of immunoinhibitory activities on diverse immune cells. Characterization of ebvIL-10 and several mutants, expressed in Escherichia coli, by gel filtration chromatography and mass spectrometry revealed a +1 frameshift upon ebvIL-10 expression. The frameshift is caused by the rare AGG codon at ebvIL-10 Arg159, which is followed by the most inefficient stop signal, UGAC. The frameshift was corrected by substituting the rare AGG codon with an abundant arginine codon, CGU, or by enhancing the level of tRNA that decodes the AGG codon. As a result, ebvIL-10 expression levels increased by approximately 3-fold and the purity of the protein improved from 85-95% to 98-99%. The correction of the frameshift has been essential for continuing structural and biophysical studies of ebvIL-10.

Amino Acid Sequence↗
PubMed1992

Cell-free translation systems from different eukaryotes differ in their sensitivity to a template sugar-phosphate backbone.

To study the role of a messenger sugar-phosphate backbone in the ribosomal decoding process, poly(U) and poly(dT) template activity in different eukaryotic systems has been compared. 80S ribosomes from Saccharomyces cerevisiae appeared to be able to translate poly(dT) both in the presence and in the absence of elongation factors, contrary to poly(U). However, ribosomes from higher eukaryotes (wheat germ, rabbit liver) are completely inefficient in poly(dT) translation. Moreover, rabbit liver ribosomes fail to bind effectively phenylalanyl-tRNA in the presence of poly(dT) although the polynucleotide seems to interact with the ribosomal decoding center. It is also of particular interest that hybrid ribosomes formed from the yeast and rabbit liver subunits can translate poly(dT) only when the large ribosomal subunit from yeast is used.

Animals↗
PubMed1999

RNA editing in Arabidopsis mitochondria effects 441 C to U changes in ORFs.

On the basis of the sequence of the mitochondrial genome in the flowering plant Arabidopsis thaliana, RNA editing events were systematically investigated in the respective RNA population. A total of 456 C to U, but no U to C, conversions were identified exclusively in mRNAs, 441 in ORFs, 8 in introns, and 7 in leader and trailer sequences. No RNA editing was seen in any of the rRNAs or in several tRNAs investigated for potential mismatch corrections. RNA editing affects individual coding regions with frequencies varying between 0 and 18.9% of the codons. The predominance of RNA editing events in the first two codon positions is not related to translational decoding, because it is not correlated with codon usage. As a general effect, RNA editing increases the hydrophobicity of the coded mitochondrial proteins. Concerning the selection of RNA editing sites, little significant nucleotide preference is observed in their vicinity in comparison to unedited C residues. This sequence bias is, per se, not sufficient to specify individual C nucleotides in the total RNA population in Arabidopsis mitochondria.

Arabidopsis↗
PubMed2006

Temporal shape error concealment by global motion compensation with local refinement.

This paper presents an original temporal shape error concealment technique based on a combination of global and local motion compensation. For this technique, which is especially useful for object-based video applications in error-prone environments (e.g., mobile networks), it is assumed that the shape of the corrupted object at hand is in the form of a binary alpha plane and some of the shape data is missing due to channel errors. To conceal the corrupted shape, the decoder first assumes that a global motion model can describe the shape changes in consecutive time instants. This way, based on locally estimated global motion parameters, the decoder attempts to conceal the corrupted alpha plane by global motion compensating the shape data from the previous time instant. Afterwards, since a global motion model cannot perfectly describe all alpha plane changes, a local motion refinement is applied to improve the concealment in areas of the object with significant local motion.

Algorithms↗
PubMed2001

Molecular detection of prostate cancer in urine by GSTP1 hypermethylation.

Novel approaches for the early detection and management of prostate cancer are urgently needed. Clonal genetic alterations have been used as targets for the detection of neoplastic cells in bodily fluids from many cancer types. A similar strategy for molecular diagnosis of prostate cancer requires a common and/or early genetic alteration as a specific target for neoplastic prostate cells. Hypermethylation of regulatory sequences at the glutathione S-transferase pi (GSTP1) gene locus is found in the majority (>90%) of primary prostate carcinomas, but not in normal prostatic tissue or other normal tissues. We hypothesized that urine from prostate cancer patients might contain shed neoplastic cells or debris amenable to DNA analysis. Matched specimens of primary tumor, peripheral blood lymphocytes (normal control), and simple voided urine were collected from 28 patients with prostate cancer of a clinical stage amenable to cure. Genomic DNA was isolated from the samples, and the methylation status of GSTP1 was examined in a blinded manner using methylation-specific PCR. Decoding of the results revealed that 22 of 28 (79%) prostate tumors were positive for GSTP1 methylation. In 6 of 22 (27%) cases, the corresponding urine-sediment DNA was positive for GSTP1 methylation, indicating the presence of neoplastic DNA in the urine. Furthermore, there was no case where urine-sediment DNA harbored methylation when the corresponding tumor was negative. Although we only detected GSTP1 methylation in under one-third of voided urine samples, we have demonstrated that molecular diagnosis of prostate neoplasia in urine is feasible. Larger studies focusing on carcinoma size, location in the prostate, and urine collection techniques, as well as more sensitive technology, may lead to the useful application of GSTP1 hypermethylation in prostate cancer diagnosis and management.

DNA Methylation↗
PubMed2004

Conserved selenoprotein synthesis is not critical for oxidative stress defence and the lifespan of Drosophila.

Selenoprotein synthesis is conserved from bacteria to man. It involves the differential decoding of the UGA stop codon as selenocysteine. The proteomes of both prokaryotes and eukaryotes, with the exception of yeast, contain only few selenoproteins. This low number is explained by a counterselection of readily oxidized selenocysteine after the introduction of oxygen into the atmosphere and the need to conserve selenoenzymes that control redox homeostasis of cells. Lack of selenoprotein synthesis in vertebrates impairs the oxidative stress defence and causes lethality. Here we show that Drosophila mutants that lack the translation elongation factor SelB/eEFsec fail to decode the UGA codon as selenocysteine, but they are viable and fertile. Oxidative stress responses and the lifespan of these flies are not affected. Protecting cells from oxidative stress can therefore not account for the selection pressure that conserves selenoprotein biosynthesis during the course of evolution.

Alleles↗
PubMed1998

A novel wobble rule found in starfish mitochondria. Presence of 7-methylguanosine at the anticodon wobble position expands decoding capability of tRNA.

In the starfish mitochondrial (mt) genome, codons AGA and AGG (in addition to AGU and AGC) have been considered to be translated as serine. There is, however, only a single candidate mt tRNA gene responsible for translating these codons and it has a GCT anticodon sequence, but guanosine at the first position of the anticodon should base pair only with pyrimidines according to the conventional wobble rule. To solve this enigma, the mt tRNA GCUser was purified, and sequence determination in combination with electrospray liquid chromatography/mass spectrometry revealed that 7-methylguanosine is located at the first position of the anticodon. This is the first case in which a tRNA has been found to have 7-methylguanosine at the wobble position. It is suggested that methylation at N-7 of wobbling guanosine endows the tRNA with the capability of forming base pairs with all four nucleotides, A, U, G, and C, and expands the repertoire of codon-anticodon interaction. This finding indicates that a nonuniversal genetic code in starfish has been generated by base modification in the tRNA anticodon.

Animals↗
PubMed2005

Independent binding sites of small protein B onto transfer-messenger RNA during trans-translation.

Stalled bacterial ribosomes are freed by transfer-messenger RNA (tmRNA). With the help of small protein B (SmpB), protein synthesis restarts and tmRNA adds a tag to the stalled protein for destruction. The conformation of a 347 nt long tmRNA from a thermophile and its interactions with SmpB were monitored using structural probes. The RNA is highly folded, including the reading frame, with <30% of unpaired residues. Footprints between SmpB and tmRNA are in the elbow of the tRNA domain, in some pseudoknots including one essential for function and in the lower part of the stem exiting the tRNA domain. The footprints outside the tRNA domain are scattered onto the tmRNA sequence, but form a cluster onto its tertiary structure derived from cryo-EM data. Some footprints flank the first triplet to be translated in tmRNA, suggesting that SmpB participates in the insertion of the tmRNA-encoded reading frame into the decoding center. To discriminate between a conformational rearrangement of tmRNA and independent binding sites, surface plasmon resonance was used and has identified three independent binding sites of SmpB on the RNA, including the site on the tRNA domain. Accordingly, SmpB is proposed to move on the tmRNA scaffold during trans-translation.

Base Sequence↗
PubMed2002

Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome.

BACKGROUND: It is widely accepted that comparative sequence data can aid the functional annotation of genome sequences; however, the most informative species and features of genome evolution for comparison remain to be determined. RESULTS: We analyzed conservation in eight genomic regions (apterous, even-skipped, fushi tarazu, twist, and Rhodopsins 1, 2, 3 and 4) from four Drosophila species (D. erecta, D. pseudoobscura, D. willistoni, and D. littoralis) covering more than 500 kb of the D. melanogaster genome. All D. melanogaster genes (and 78-82% of coding exons) identified in divergent species such as D. pseudoobscura show evidence of functional constraint. Addition of a third species can reveal functional constraint in otherwise non-significant pairwise exon comparisons. Microsynteny is largely conserved, with rearrangement breakpoints, novel transposable element insertions, and gene transpositions occurring in similar numbers. Rates of amino-acid substitution are higher in uncharacterized genes relative to genes that have previously been studied. Conserved non-coding sequences (CNCSs) tend to be spatially clustered with conserved spacing between CNCSs, and clusters of CNCSs can be used to predict enhancer sequences. CONCLUSIONS: Our results provide the basis for choosing species whose genome sequences would be most useful in aiding the functional annotation of coding and cis-regulatory sequences in Drosophila. Furthermore, this work shows how decoding the spatial organization of conserved sequences, such as the clustering of CNCSs, can complement efforts to annotate eukaryotic genomes on the basis of sequence conservation alone.

Animals↗
PubMed2006

From hype to mothballs in four years: troubles in the development of large-scale DNA biobanks in Europe.

This paper analyses the difficulties experienced by three large European DNA biobanks. The first, Icelandic-based deCode, generated immense commercial interest and intense ethical controversy. As a biotechnology company, deCode succeeded, but the Icelandic Health Sector Data Base failed. The second firm, Swedish UmanGenomics, marketed itself as the 'ethical' biotech company. Management problems including the inadequate recognition of intellectual property issues led to the company failing to secure adequate investment. The third and largest, UK Biobank, has, as a non-profit organization, not experienced these problems. But when the product - bio information--is marketed, the issue of ethically acceptable purchasers could well become contentious.

Computational Biology↗
PubMed2000

Schizophrenia as the price that homo sapiens pays for language: a resolution of the central paradox in the origin of the species.

The central paradox of schizophrenia is that the condition, apparently genetic in origin, persists in spite of a substantial fecundity disadvantage. The hypothesis is proposed that the predisposition to schizophrenia is a component of Homo sapiens-specific variation associated with the capacity for language. A genetic change (the 'speciation event', predicted to be related to the Xq21.3 to Yp chromosomal transposition that separates Homo sapiens from the great apes) allowed the hemispheres to develop with a 'cerebral torque', reflected particularly in association cortex, from right frontal to left occipital. Variations in the dimension of lateralization are associated with differences in the rate at which verbal and non-verbal ability develops. The nuclear symptoms of schizophrenia can be understood as a failure to establish dominance for a key component - the phonological sequence - of language in one hemisphere, with consequent disruption of the mechanism of 'indexicality' that allows the speaker to distinguish his thoughts from the speech output that he generates and the speech input that he receives and decodes from others.

Animals↗
PubMed2026

The role of ferroptosis in juvenile idiopathic arthritis: Causal inference and mediation by immune phenotypes.

This study employed a bidirectional 2-step, two-sample Mendelian randomization approach to investigate the causal relationships between ferroptosis-related genes and juvenile idiopathic arthritis (JIA) and to explore the mediating role of immune cells. Ferroptosis genes were identified from the deCODE database and matched with protein quantitative trait locus data as exposures to evaluate their causal effects on JIA, while immune cell traits were similarly assessed. For genes showing positive Mendelian randomization results, further analyses were conducted to determine whether immune cells mediated the effects on JIA, with mediation analysis performed only in the presence of causal associations. Data were sourced from the GWAS, FerrDb, and other public repositories. Nine ferroptosis-related genes were found to have causal links with JIA: HSPB1, DECR1, LIFR, and CTSB increased JIA risk, whereas PIEZO1, DPP4, BID, and others were protective. Forty immune cell traits were also causally associated with JIA. Mediation analysis revealed that several immune cells, including CD127- CD8+ T cells, partially mediated the genetic effects, with mediation proportions reaching up to 18.6%. Collectively, these results point to a ferroptosis-immune-JIA axis, suggesting that ferroptosis-related genes contribute to JIA pathogenesis through immune cell mediation and offering new mechanistic insights and potential therapeutic targets.

Arthritis, Juvenile↗
PubMed2025

Decoding missense variants pleiotropy in the immune GPCR P2RY8.

G protein-coupled receptors (GPCRs) form the largest family of cell surface receptors and remain a central focus in pharmacology and drug discovery. Despite extensive structural and pharmacological studies, the functional impact of missense variation across GPCRs remains poorly understood, particularly for receptors involved in immune regulation. In this issue of Cell Genomics, LaFlam et al.1 systematically map P2RY8 variant functions using deep mutational scanning (DMS) combined with structural biology approaches, revealing pleiotropy and mechanisms linking GPCR variation to B cell confinement and lymphoma.

Humans↗
PubMed1991

The path of mRNA through the Escherichia coli ribosome; site-directed cross-linking of mRNA analogues carrying a photo-reactive label at various points 3' to the decoding site.

mRNA analogues approximately 40 bases long were prepared by T7 transcription from synthetic DNA templates. Each message contained the sequence ACC-GCG (coding for threonine and alanine, respectively), together with a single thio-U residue located at a variable position on the 3'-side of these coding triplets. The thio-U residue was either substituted with 4-azidophenacyl bromide to introduce a photo-reactive group, or was left unsubstituted for direct UV cross-linking. After binding to Escherichia coli 70S ribosomes in the presence of tRNA-Thr or tRNA-Ala, the thio-U residue or azidophenyl group was photo-activated and the products of cross-linking (which was exclusively to the 30S subunit) were analysed. Immunological analysis of the cross-linked proteins showed that S5 and S3, together with S1, were the targets of cross-linking at positions close to the decoding site, with the cross-linking to S3 and S1 persisting at positions further away. Analysis of the 16S RNA showed cross-links to the region of bases 1390-1400 in all cases, but in one instance (with the reactive nucleotide 11 bases from the decoding site) simultaneous cross-linking was observed to the latter region and to position 532; these two RNA regions are far apart in current three-dimensional models of the 30S subunit.

Amino Acid Sequence↗
PubMed2003

CDS annotation in full-length cDNA sequence.

The identification of coding sequences (CDS) is an important step in the functional annotation of genes. CDS prediction for mammalian genes from genomic sequence is complicated by the vast abundance of intergenic sequence in the genome, and provides little information about how different parts of potential CDS regions are expressed. In contrast, mammalian gene CDS prediction from cDNA sequence offers obvious advantages, yet encounters a different set of complexities when performed on high-throughput cDNA (HTC) sequences, such as the set of 60,770 cDNAs isolated from full-length enriched libraries of the FANTOM2 project. We developed a CDS annotation strategy that uses a variety of different CDS prediction programs to annotate the CDS regions of FANTOM2 cDNAs. These include rsCDS, which uses sequence similarity to known proteins; ProCrest; Longest-ORF and Truncated-ORF, which are ab initio based predictors; and finally, DECODER and NCBI CDS predictor, which use a combination of both principles. Aided by graphical displays of these CDS prediction results in the context of other sequence similarity results for each cDNA, FANTOM2 CDS inspection by curators and follow-up quality control procedures resulted in high quality CDS predictions for a total of 14,345 FANTOM2 clones.

Animals↗
PubMedDate not supplied

[Why does the DNA code contain 4 letters?].

The answer to this question is not yet known. There are two ways to express information, i.e., to reduce the number of letters in alphabet (n), which simplifies the decoding machine, but leads to longer informational sequences, or to increase n, which shortens sequences, but complicates the informational machine. The compromise between these two possibilities would be to obtain the minimum of one of summary informational component's parameters. The summary component is the sum of corresponding decoding machine's and the program's parameters. In this work it was demonstrated that DNA four-letter code is optimal, for it allows the minimal volume of summary cell informational contents. But it is so only for the most simple DNA. Our calculations may indirectly show that such DNA (and not more complicated) was the object of "projecting" at one of the biological evolution's early stages.

Amino Acid Sequence↗