Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RefSeq curation and annotation of stop codon recoding in vertebrates.

ABSTRACT: Recoding of stop codons as amino acid-specifying codons is a co-translational event that enables C-terminal extension of a protein. Synthesis of selenoproteins requires recoding of internal UGA stop codons to the 21st non-standard amino acid selenocysteine (Sec) and plays a vital role in human health and disease. Separately, canonical stop codons can be recoded to specify standard amino acids in a process known as stop codon readthrough (SCR), producing extended protein isoforms with potential novel functions. Conventional computational tools cannot distinguish between the dual functionality of stop codons as stop signals and sense codons, resulting in misannotation of selenoprotein gene products and failure to predict SCR. Manual curation is therefore required to correctly represent recoded gene products and their functions. Our goal was to provide accurately curated and annotated datasets of selenoprotein and SCR transcript and protein records to serve as annotation standards and to promote basic and biomedical research. Gene annotations were curated in nine vertebrate model organisms and integrated into NCBI's Reference Sequence (RefSeq) dataset, resulting in 247 selenoprotein genes encoding 322 selenoproteins, and 93 genes exhibiting SCR encoding 94 SCR isoforms.

SUBMITTER: Rajput B

PROVIDER: S-EPMC6344875 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

RefSeq curation and annotation of antizyme and antizyme inhibitor genes in vertebrates.

Project description:Polyamines are ubiquitous cations that are involved in regulating fundamental cellular processes such as cell growth and proliferation; hence, their intracellular concentration is tightly regulated. Antizyme and antizyme inhibitor have a central role in maintaining cellular polyamine levels. Antizyme is unique in that it is expressed via a novel programmed ribosomal frameshifting mechanism. Conventional computational tools are unable to predict a programmed frameshift, resulting in misannotation of antizyme transcripts and proteins on transcript and genomic sequences. Correct annotation of a programmed frameshifting event requires manual evaluation. Our goal was to provide an accurately curated and annotated Reference Sequence (RefSeq) data set of antizyme transcript and protein records across a broad taxonomic scope that would serve as standards for accurate representation of these gene products. As antizyme and antizyme inhibitor proteins are functionally connected, we also curated antizyme inhibitor genes to more fully represent the elegant biology of polyamine regulation. Manual review of genes for three members of the antizyme family and two members of the antizyme inhibitor family in 91 vertebrate organisms resulted in a total of 461 curated RefSeq records.

| S-EPMC4551939 | biostudies-literature

RefSeq: an update on prokaryotic genome annotation and curation.

Project description:The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) provides annotation for over 95 000 prokaryotic genomes that meet standards for sequence quality, completeness, and freedom from contamination. Genomes are annotated by a single Prokaryotic Genome Annotation Pipeline (PGAP) to provide users with a resource that is as consistent and accurate as possible. Notable recent changes include the development of a hierarchical evidence scheme, a new focus on curating annotation evidence sources, the addition and curation of protein profile hidden Markov models (HMMs), release of an updated pipeline (PGAP-4), and comprehensive re-annotation of RefSeq prokaryotic genomes. Antimicrobial resistance proteins have been reannotated comprehensively, improved structural annotation of insertion sequence transposases and selenoproteins is provided, curated complex domain architectures have given upgraded names to millions of multidomain proteins, and we introduce a new kind of annotation rule-BlastRules. Continual curation of supporting evidence, and propagation of improved names onto RefSeq proteins ensures that the functional annotation of genomes is kept current. An increasing share of our annotation now derives from HMMs and other sets of annotation rules that are portable by nature, and available for download and for reuse by other investigators. RefSeq is found at https://www.ncbi.nlm.nih.gov/refseq/.

| S-EPMC5753331 | biostudies-literature

Regulation of gene expression by stop codon recoding: selenocysteine.

Project description:The regulation of gene expression at the translational level not only allows for rapid changes in specific protein levels but also provides an opportunity to alter codon specificity. For the incorporation of selenocysteine (Sec) into protein, the UGA codon is transformed from one that signals translation termination to one specific for Sec. This review provides a look at Sec incorporation from the perspective of the individual steps involved in protein synthesis: initiation, elongation and termination. The roles of the factors known to be required for Sec incorporation are considered in the context of each step in translation including structural modeling of the differences between the standard elongation factor eEF1A and the Sec-specific counterpart, eEFSec.

| S-EPMC2820279 | biostudies-literature

RefSeq: expanding the Prokaryotic Genome Annotation Pipeline reach with protein family model curation.

Project description:The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) contains nearly 200 000 bacterial and archaeal genomes and 150 million proteins with up-to-date annotation. Changes in the Prokaryotic Genome Annotation Pipeline (PGAP) since 2018 have resulted in a substantial reduction in spurious annotation. The hierarchical collection of protein family models (PFMs) used by PGAP as evidence for structural and functional annotation was expanded to over 35 000 protein profile hidden Markov models (HMMs), 12 300 BlastRules and 36 000 curated CDD architectures. As a result, >122 million or 79% of RefSeq proteins are now named based on a match to a curated PFM. Gene symbols, Enzyme Commission numbers or supporting publication attributes are available on over 40% of the PFMs and are inherited by the proteins and features they name, facilitating multi-genome analyses and connections to the literature. In adherence with the principles of FAIR (findable, accessible, interoperable, reusable), the PFMs are available in the Protein Family Models Entrez database to any user. Finally, the reference and representative genome set, a taxonomically diverse subset of RefSeq prokaryotic genomes, is now recalculated regularly and available for download and homology searches with BLAST. RefSeq is found at https://www.ncbi.nlm.nih.gov/refseq/.

| S-EPMC7779008 | biostudies-literature

Partitioning between recoding and termination at a stop codon-selenocysteine insertion sequence.

Project description:Selenocysteine (Sec) is inserted into proteins by recoding a UGA stop codon followed by a selenocysteine insertion sequence (SECIS). UGA recoding by the Sec machinery is believed to be very inefficient owing to RF2-mediated termination at UGA. Here we show that recoding efficiency in vivo is 30-40% independently of the cell growth rate. Efficient recoding requires sufficient selenium concentrations in the medium. RF2 is an unexpectedly poor competitor of Sec. We recapitulate the major characteristics of SECIS-dependent UGA recoding in vitro using a fragment of fdhF-mRNA encoding a natural bacterial selenoprotein. Only 40% of actively translating ribosomes that reach the UGA codon insert Sec, even in the absence of RF2, suggesting that the capacity to insert Sec into proteins is inherently limited. RF2 does not compete with the Sec incorporation machinery; rather, it terminates translation on those ribosomes that failed to incorporate Sec. The data suggest a model in which early recruitment of Sec-tRNA(Sec)-SelB-GTP to the SECIS blocks the access of RF2 to the stop codon, thereby prioritizing recoding over termination at Sec-dedicated stop codons.

| S-EPMC4513850 | biostudies-literature

Widespread stop-codon recoding in bacteriophages may regulate translation of lytic genes.

Project description:Bacteriophages (phages) are obligate parasites that use host bacterial translation machinery to produce viral proteins. However, some phages have alternative genetic codes with reassigned stop codons that are predicted to be incompatible with bacterial translation systems. We analysed 9,422 phage genomes and found that stop-codon recoding has evolved in diverse clades of phages that infect bacteria present in both human and animal gut microbiota. Recoded stop codons are particularly over-represented in phage structural and lysis genes. We propose that recoded stop codons might function to prevent premature production of late-stage proteins. Stop-codon recoding has evolved several times in closely related lineages, which suggests that adaptive recoding can occur over very short evolutionary timescales.

| S-EPMC9197471 | biostudies-literature

ENVIRONMENT MODULATES PROTEIN HETEROGENEITY THROUGH TRANSCRIPTIONAL AND TRANSLATIONAL STOP CODON RECODING

Project description:In order to systematically assess the frequency and origin of stop codon recoding events, we designed a library of reporters. We introduced premature stop codons into mScarlet that enabled high-throughput quantification of protein synthesis termination errors in E. coli using fluorescent microscopy. We found that under stress conditions, stop codon recoding may occur with a rate as high as 80%, depending on the nucleotide context, suggesting that evolution frequently samples stop codon recoding events. The analysis of selected reporters by mass spectrometry and RNA-seq showed that not only translation but also transcription errors contribute to stop codon recoding. The RNA polymerase is more likely to misincorporate a nucleotide at premature stop codons. Proteome-wide detection of stop codon recoding by mass spectrometry revealed that temperature regulates the expression of cryptic sequences generated by stop codon recoding in E. coli. Overall, our findings suggest that the environment influences the accuracy of protein production which increases protein heterogeneity when the organisms need to adapt to new conditions.

2024-03-28 | GSE226936 | GEO

Predicting stop codon reassignment improves functional annotation of bacteriophages.

Project description:The majority of bacteriophage diversity remains uncharacterised, and new intriguing mechanisms of their biology are being continually described. Members of some phage lineages, such as the Crassvirales, repurpose stop codons to encode an amino acid by using alternate genetic codes. Here, we investigated the prevalence of stop codon reassignment in phage genomes and subsequent impacts on functional annotation. We predicted 76 genomes within INPHARED and 712 vOTUs from the Unified Human Gut Virome catalogue (UHGV) that repurpose a stop codon to encode an amino acid. We re-annotated these sequences with modified versions of Pharokka and Prokka, called Pharokka-gv and Prokka-gv, to automatically predict stop codon reassignment prior to annotation. Both tools significantly improved the quality of annotations, with Pharokka-gv performing best. For sequences predicted to repurpose TAG to glutamine (translation table 15), Pharokka-gv increased the median gene length (median of per genome medians) from 287 to 481 bp for UHGV sequences (67.8% increase) and from 318 to 550 bp for INPHARED sequences (72.9% increase). The re-annotation increased mean coding density from 66.8% to 90.0%, and from 69.0% to 89.8% for UHGV and INPHARED sequences. Furthermore, the proportion of genes that could be assigned functional annotation increased, including an increase in the number of major capsid proteins that could be identified. We propose that automatic prediction of stop codon reassignment before annotation is beneficial to downstream viral genomic and metagenomic analyses.

| S-EPMC10769273 | biostudies-literature

Driving through stop signs: predicting stop codon reassignment improves functional annotation of bacteriophages

Project description: Not available

| S-EPMC11210395 | biostudies-literature

Mouse genome annotation by the RefSeq project.

Project description:Complete and accurate annotation of the mouse genome is critical to the advancement of research conducted on this important model organism. The National Center for Biotechnology Information (NCBI) develops and maintains many useful resources to assist the mouse research community. In particular, the reference sequence (RefSeq) database provides high-quality annotation of multiple mouse genome assemblies using a combinatorial approach that leverages computation, manual curation, and collaboration. Implementation of this conservative and rigorous approach, which focuses on representation of only full-length and non-redundant data, produces high-quality annotation products. RefSeq records explicitly link sequences to current knowledge in a timely manner, updating public records regularly and rapidly in response to nomenclature updates, addition of new relevant publications, collaborator discussion, and user feedback. Whole genome re-annotation is also conducted at least every 12-18 months, and often more frequently in response to assembly updates or availability of informative data. This article highlights key features and advantages of RefSeq genome annotation products and presents an overview of NCBI processes to generate these data. Further discussion of NCBI's resources highlights useful features and the best methods for accessing our data.

| S-EPMC4602073 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data