Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5’UTRs DOI Creative Commons

Caroline Meguerditchian,

David Baux, Thomas Ludwig

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 10, 2024

Abstract Non-canonical small Open Reading Frames (sORFs) are among main regulators of gene expression. The most studied ones upstream ORFs (upORFs) located in the 5’UTR coding genes. Internal (intORFs) sequence and downstream (dORFs) 3’UTR have received less attention. Different bioinformatics tools permit to predict single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool non-canonical translation initiation sites intORFs dORFs. We propose an upgrade our MORFEE identify SNVs that may alter all types sORFs transcripts from a VCF file. Moreover, we generate exhaustive catalog, named MORFEEdb, reporting possible existing upORFs new human provide R script for visualizing results. MORFEEdb has been implemented public platform Mobidetails. Finally, annotation ClinVar with reveals more than 45% UTR-SNVs can In conclusion, potential improve molecular diagnosis rare diseases facilitate identification functional genome-wide association studies complex traits.

Язык: Английский

Structural Features of 5′ Untranslated Region in Translational Control of Eukaryotes DOI Open Access
Elizaveta A. Razumova,

Aleksandr Makariuk,

Olga А. Dontsova

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1979 - 1979

Опубликована: Фев. 25, 2025

Gene expression is a complex process regulated at multiple levels in eukaryotic cells. Translation frequently represents pivotal step the control of gene expression. Among stages translation, initiation particularly important, as it governs ribosome recruitment and efficiency protein synthesis. The 5' untranslated region (5' UTR) mRNA plays key role this process, often exhibiting complicated structured landscape. Numerous mRNAs possess long UTRs that contain diverse regulatory elements, including RNA secondary structures, specific nucleotide motifs, chemical modifications. These structural features can independently modulate translation through their intrinsic properties or by serving platforms for trans-acting factors such RNA-binding proteins. dynamic nature UTR elements allows cells to fine-tune response environmental cellular signals. Understanding these mechanisms not only fundamental molecular biology but also holds significant biomedical potential. Insights into UTR-mediated regulation could drive advancements synthetic mRNA-based targeted therapies. This review outlines current knowledge UTR, interplay between them, combined functional impact on translation.

Язык: Английский

Процитировано

0

Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5'UTRs. DOI

Caroline Meguerditchian,

David Baux, Thomas Ludwig

и другие.

PubMed, Год журнала: 2025, Номер 7(1), С. lqaf017 - lqaf017

Опубликована: Март 1, 2025

Non-canonical small open reading frames (sORFs) are among the main regulators of gene expression. The most studied these upstream ORFs (upORFs) located in 5'-untranslated region (UTR) coding genes. Internal (intORFs) sequence and downstream (dORFs) 3'UTR have received less attention. Different bioinformatics tools permit prediction single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool predicts non-canonical translation initiation sites intORFs dORFs. We propose an upgrade our MORFEE to identify SNVs that may alter all types sORFs transcripts from a VCF file. Moreover, we generate exhaustive catalog, named MORFEEdb, reporting possible existing upORFs new ones human transcripts, provide R script for visualizing results. MORFEEdb has been implemented public platform Mobidetails. Finally, annotation ClinVar with reveals > 45% UTR-SNVs can In conclusion, potential improve molecular diagnosis rare diseases facilitate identification functional genome-wide association studies complex traits.

Язык: Английский

Процитировано

0

LncRNAs Ride the Storm of Epigenetic Marks DOI Open Access
Giulia Gaggi,

Clinton Hausman,

Soomin Cho

и другие.

Genes, Год журнала: 2025, Номер 16(3), С. 313 - 313

Опубликована: Март 6, 2025

Advancements in genome sequencing technologies have uncovered the multifaceted roles of long non-coding RNAs (lncRNAs) human cells. Recent discoveries identified lncRNAs as major players gene regulatory pathways, highlighting their pivotal role cell growth and development. Their dysregulation is implicated onset genetic disorders age-related diseases, including cancer. Specifically, they been found to orchestrate molecular mechanisms impacting epigenetics, DNA methylation hydroxymethylation, histone modifications, chromatin remodeling, thereby significantly influencing expression. This review provides an overview current knowledge on lncRNA-mediated epigenetic regulation expression, emphasizing biomedical implications development different types cancers diseases.

Язык: Английский

Процитировано

0

Mutational constraint analysis workflow for overlapping short open reading frames and genomic neighbors DOI Creative Commons
Martin Danner, Matthias Begemann, Florian Kraft

и другие.

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 14, 2025

Abstract Understanding the dark genome is a priority task following complete sequencing of human genome. Short open reading frames (sORFs) are group largely unexplored elements with potential for being translated into microproteins. The definitive number coding and regulatory sORFs not known, however they could account up to 1–2% This corresponds an order magnitude in range canonical genes. For few clinical relevance has already been demonstrated, but majority biological function remains unclear. A major limitation predicting their disease using large-scale genomic data fact that no population-level constraint metrics genetic variants yet available. To overcome this, we used recently released gnomAD 4.0 dataset analyzed consensus set neighbors. We demonstrate mostly embedded moderately constrained context, within gencode identified subset highly comparable

Язык: Английский

Процитировано

0

RIBOSS detects novel translational events by combining long- and short-read transcriptome and translatome profiling DOI Creative Commons
Chun Shen Lim,

Alexandra K Gibbon,

A. D. Nguyen

и другие.

Briefings in Bioinformatics, Год журнала: 2025, Номер 26(2)

Опубликована: Март 1, 2025

Ribosome profiling is a high-throughput sequencing technique that captures the positions of translating ribosomes on RNAs. Recent advancements in ribosome include achieving highly phased footprints for plant translatomes and more recently bacterial translatomes. This substantially increases specificity detecting open reading frames (ORFs) can be translated, such as small ORFs located upstream downstream annotated ORFs. However, most genomes (e.g. genomes) lack annotations transcription start termination sites. hinders systematic discovery novel 'untranslated' regions data. Here, we develop new computational pipeline called RIBOSS to discover noncanonical assess their translational potential against The Python modules are versatile, use them analyse both prokaryotic eukaryotic We present resulting list with high Homo sapiens, Arabidopsis thaliana, Salmonella enterica. further illustrate utility when studying organisms incomplete transcriptome annotations. leverage long-read short-read data reference-guided assembly events assembled S. In sum, first integrated ORF detection assessment incorporates long- technologies investigate translation. freely available at https://github.com/lcscs12345/riboss.

Язык: Английский

Процитировано

0

Editorial: Translational control in cancer DOI Creative Commons
Francesca Aguiló, Erik Dassi

NAR Cancer, Год журнала: 2024, Номер 6(3)

Опубликована: Июль 9, 2024

Процитировано

0

Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5’UTRs DOI Creative Commons

Caroline Meguerditchian,

David Baux, Thomas Ludwig

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 10, 2024

Abstract Non-canonical small Open Reading Frames (sORFs) are among main regulators of gene expression. The most studied ones upstream ORFs (upORFs) located in the 5’UTR coding genes. Internal (intORFs) sequence and downstream (dORFs) 3’UTR have received less attention. Different bioinformatics tools permit to predict single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool non-canonical translation initiation sites intORFs dORFs. We propose an upgrade our MORFEE identify SNVs that may alter all types sORFs transcripts from a VCF file. Moreover, we generate exhaustive catalog, named MORFEEdb, reporting possible existing upORFs new human provide R script for visualizing results. MORFEEdb has been implemented public platform Mobidetails. Finally, annotation ClinVar with reveals more than 45% UTR-SNVs can In conclusion, potential improve molecular diagnosis rare diseases facilitate identification functional genome-wide association studies complex traits.

Язык: Английский

Процитировано

0