Alternative ORFs and small ORFs: shedding light on the dark proteome

Nucleic Acids Research, Год журнала: 2019, Номер 48(3), С. 1029 - 1042

Опубликована: Авг. 15, 2019

Abstract Traditional annotation of protein-encoding genes relied on assumptions, such as one open reading frame (ORF) encodes protein and minimal lengths for translated proteins. With the serendipitous discoveries ORFs encoded upstream downstream annotated ORFs, from alternative start sites nested within RNAs previously considered noncoding, it is becoming clear that these initial assumptions are incorrect. The findings have led to realization genetic information more densely coded proteome complex than anticipated. As such, interest in identification characterization ignored ‘dark proteome’ increasing, though we note research eukaryotes bacteria has largely progressed isolation. To bridge this gap illustrate exciting emerging studies dark proteome, highlight recent advances both eukaryotic bacterial cells. We discuss progress detection well understanding functions regulation their expression posit questions future work.

Язык: Английский

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Standardized annotation of translated open reading frames

Nature Biotechnology, Год журнала: 2022, Номер 40(7), С. 994 - 999

Опубликована: Июль 1, 2022

Язык: Английский

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Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames

Molecular Cell, Год журнала: 2023, Номер 83(6), С. 994 - 1011.e18

Опубликована: Фев. 17, 2023

All species continuously evolve short open reading frames (sORFs) that can be templated for protein synthesis and may provide raw materials evolutionary adaptation. We analyzed the origins of 7,264 recently cataloged human sORFs found most were evolutionarily young had emerged de novo. additionally identified 221 previously missed potentially translated into peptides up to 15 amino acids—all which are smaller than smallest microprotein annotated date. To investigate bioactivity sORF-encoded small microproteins, we subjected 266 candidates a mass-spectrometry-based interactome screen with motif resolution. Based on these interactomes additional cellular assays, associate several mRNA splicing, translational regulation, endocytosis. Our work provides insights interaction potential proteins, thereby helping elucidate this underexplored territory proteome.

Язык: Английский

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Evolution and implications of de novo genes in humans

Nature Ecology & Evolution, Год журнала: 2023, Номер 7(6), С. 804 - 815

Опубликована: Март 16, 2023

Язык: Английский

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LncRNA-encoded peptides in cancer

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 12, 2024

Long non-coding RNAs (lncRNAs), once considered transcriptional noise, have emerged as critical regulators of gene expression and key players in cancer biology. Recent breakthroughs revealed that certain lncRNAs can encode small open reading frame (sORF)-derived peptides, which are now understood to contribute the pathogenesis various cancers. This review synthesizes current knowledge on detection, functional roles, clinical implications lncRNA-encoded peptides cancer. We discuss technological advancements detection validation sORFs, including ribosome profiling mass spectrometry, facilitated discovery these peptides. The roles processes such transcription, translation regulation, signal transduction, metabolic reprogramming explored types potential is highlighted, with a focus their utility diagnostic biomarkers, prognostic indicators, therapeutic targets. challenges future directions translating findings into practice also discussed, need for large-scale validation, development sensitive methods, optimization peptide stability delivery.

Язык: Английский

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Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF

Protein Science, Год журнала: 2025, Номер 34(2)

Опубликована: Янв. 22, 2025

Abstract Biochemistry textbooks describe eukaryotic mRNAs as monocistronic. However, increasing evidence reveals the widespread presence and translation of upstream open reading frames preceding “main” ORF. DNA RNA viruses infecting eukaryotes often produce polycistronic have evolved multiple ways manipulating host's machinery. Here, we introduce an experimental model to study gene expression regulation from virus‐like bicistronic in human cells. The consists a short ORF reporter downstream encoding fluorescent protein. We engineered synonymous variants explore large parameter space, including codon usage preferences, mRNA folding features, splicing propensity. show that machinery can translate mRNAs, albeit protein levels are thousand times lower than those Furthermore, recoding exclusively during elongation significantly influences its own efficiency, cryptic splice signals, modulates probability translation. Our results consistent with leaky scanning mechanism facilitating cells, offering new insights into role ORFs regulation.

Язык: Английский

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Function and Evolution of Upstream ORFs in Eukaryotes

Trends in Biochemical Sciences, Год журнала: 2019, Номер 44(9), С. 782 - 794

Опубликована: Апрель 17, 2019

Язык: Английский

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RNAsamba: neural network-based assessment of the protein-coding potential of RNA sequences

NAR Genomics and Bioinformatics, Год журнала: 2020, Номер 2(1)

Опубликована: Янв. 13, 2020

Abstract The advent of high-throughput sequencing technologies made it possible to obtain large volumes genetic information, quickly and inexpensively. Thus, many efforts are devoted unveiling the biological roles genomic elements, being distinction between protein-coding long non-coding RNAs one most important tasks. We describe RNAsamba, a tool predict coding potential RNA molecules from sequence information using neural network-based that models both whole ORF identify patterns distinguish transcripts. evaluated RNAsamba’s classification performance transcripts coming humans several other model organisms show recurrently outperforms state-of-the-art methods. Our results also RNAsamba can signals in partial-length ORFs UTR sequences, evidencing its algorithm is not dependent on complete transcript sequences. Furthermore, small ORFs, traditionally identified with ribosome profiling experiments. believe will enable faster more accurate findings data species sequenced for first time. A user-friendly web interface, documentation containing instructions local installation usage, source code be found at https://rnasamba.lge.ibi.unicamp.br/.

Язык: Английский

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Revisiting sORFs: overcoming challenges to identify and characterize functional microproteins

FEBS Journal, Год журнала: 2021, Номер 289(1), С. 53 - 74

Опубликована: Фев. 18, 2021

Short ORFs (sORFs), that is, occurrences of a start and stop codon within 100 codons or less, can be found in organisms all domains life, outnumbering annotated protein‐coding by orders magnitude. Even though functional proteins smaller than amino acids are known, the coding potential sORFs has often been overlooked, as it is not trivial to predict test for functionality large number sORFs. Recent advances ribosome profiling mass spectrometry approaches, together with refined bioinformatic predictions, have enabled huge leap forward this field identified thousands likely A relatively low small microproteins produced from these characterized so far on molecular, structural, and/or mechanistic level. These however display versatile and, some cases, essential cellular functions, allowing exciting possibility many more, previously unknown might encoded genome, waiting discovered. This review will give an overview steadily growing microprotein field, focusing eukaryotic proteins. We discuss emerging themes molecular action microproteins, well challenges identification characterization.

Язык: Английский

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Uncovering de novo gene birth in yeast using deep transcriptomics

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Янв. 27, 2021

De novo gene origination has been recently established as an important mechanism for the formation of new genes. In organisms with a large genome, intergenic and intronic regions provide plenty raw material transcriptional events to occur, but little is know about how de transcripts originate in more densely-packed genomes. Here, we identify 213 originated Saccharomyces cerevisiae using deep transcriptomics genomic synteny information from multiple yeast species grown two different conditions. We find that half are expressed which already harbor other genes opposite orientation; these show similar expression changes response stress their overlapping counterparts, some appear translate small proteins. Thus, fraction likely co-evolve existing

Язык: Английский

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