The dark proteome: translation from noncanonical open reading frames

A platform for curated products from novel open reading frames prompts reinterpretation of disease variants

(2021) Matthew D.C. Neville et al.   GENOME RESEARCH

Potentiation of B2 receptor signaling by AltB2R, a newly identified alternative protein encoded in the human bradykinin B2 receptor gene

(2021) Maxime Gagnon et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A short ORF-encoded transcriptional regulator

(2021) Minseob Koh et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24

(2021) Xiongwen Cao et al.   Nature Communications

An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a Circuit Breaker of Lactate Metabolism

(2021) Nunu Huang et al.   Cell Metabolism

The role of micropeptides in biology

(2021) Rui Vitorino et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Noncanonical open reading frames encode functional proteins essential for cancer cell survival

(2021) John R. Prensner et al.   NATURE BIOTECHNOLOGY

Disrupting upstream translation in mRNAs is associated with human disease

(2021) David S. M. Lee et al.   Nature Communications

Determinants of genome-wide distribution and evolution of uORFs in eukaryotes

(2021) Hong Zhang et al.   Nature Communications

Most non-canonical proteins uniquely populate the proteome or immunopeptidome

(2021) Maria Virginia Ruiz Cuevas et al.   Cell Reports

Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity

(2021) Cheryl Q. E. Lee et al.   Nature Communications

A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development

(2021) Andrew J. Modzelewski et al.   CELL

The oncomicropeptide APPLE promotes hematopoietic malignancy by enhancing translation initiation

(2021) Linyu Sun et al.   MOLECULAR CELL

Overlapping genes in natural and engineered genomes

(2021) Bradley W. Wright et al.   NATURE REVIEWS GENETICS

Evidence for a novel overlapping coding sequence in POLG initiated at a CUG start codon

(2020) Yousuf A. Khan et al.   BMC GENETICS

The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function

(2020) Helen L Spencer et al.   CARDIOVASCULAR RESEARCH

Pervasive functional translation of noncanonical human open reading frames

(2020) Jin Chen et al.   SCIENCE

A Novel Micropeptide Encoded by Y-Linked LINC00278 Links Cigarette Smoking and AR Signaling in Male Esophageal Squamous Cell Carcinoma

(2020) Siqi Wu et al.   CANCER RESEARCH

Peptide SMIM30 promotes HCC development by inducing SRC/YES1 membrane anchoring and MAPK pathway activation

(2020) Yanan Pang et al.   JOURNAL OF HEPATOLOGY

Micropeptide MIAC Inhibits HNSCC Progression by Interacting with Aquaporin 2

(2020) Mengwei Li et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis

(2020) Song Zhu et al.   Nature Communications

Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes

(2020) Chloe Chong et al.   Nature Communications

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

(2020) Shan Zhang et al.   Nature Communications

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

(2020) Nicola Whiffin et al.   Nature Communications

A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation

(2020) Liman Niu et al.   Science Advances

Translation of small downstream ORFs enhances translation of canonical main open reading frames

(2020) Qiushuang Wu et al.   EMBO JOURNAL

Decoding mRNA translatability and stability from the 5′ UTR

(2020) Longfei Jia et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Unusually efficient CUG initiation of an overlapping reading frame in POLG mRNA yields novel protein POLGARF

(2020) Gary Loughran et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A high-stringency blueprint of the human proteome

(2020) Subash Adhikari et al.   Nature Communications

The FUS gene is dual‐coding with both proteins contributing to FUS ‐mediated toxicity

(2020) Marie A Brunet et al.   EMBO REPORTS

LINC00116 codes for a mitochondrial peptide linking respiration and lipid metabolism

(2019) Anastasia Chugunova et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism

(2019) Serge Hardy et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling

(2019) Xiao Zheng et al.   Molecular Cancer

Translation of upstream open reading frames in a model of neuronal differentiation

(2019) Caitlin M. Rodriguez et al.   BMC GENOMICS

The Translational Landscape of the Human Heart

(2019) Sebastiaan van Heesch et al.   CELL

A hidden human proteome encoded by ‘non-coding’ genes

(2019) Shaohua Lu et al.   NUCLEIC ACIDS RESEARCH

Ribosome profiling analysis identified a KRAS-interacting microprotein that represses oncogenic signaling in hepatocellular carcinoma cells

(2019) Wenli Xu et al.   Science China-Life Sciences

Distinct types of short open reading frames are translated in plant cells

(2019) Igor Fesenko et al.   GENOME RESEARCH

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

(2019) Mona Wu Orr et al.   NUCLEIC ACIDS RESEARCH

Micropeptide CIP 2A‐ BP encoded by LINC 00665 inhibits triple‐negative breast cancer progression

(2019) Binbin Guo et al.   EMBO JOURNAL

Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome

(2019) Philippe Cloutier et al.   JOURNAL OF PROTEOME RESEARCH

Regulation of the ER stress response by a mitochondrial microprotein

(2019) Qian Chu et al.   Nature Communications

Translated Long Non-Coding Ribonucleic Acid ZFAS1 Promotes Cancer Cell Migration by Elevating Reactive Oxygen Species Production in Hepatocellular Carcinoma

(2019) Zhi-Wei Guo et al.   Frontiers in Genetics

LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis

(2019) Yirong Wang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Accurate annotation of human protein-coding small open reading frames

(2019) Thomas F. Martinez et al.   Nature Chemical Biology

Pervasive, Coordinated Protein-Level Changes Driven by Transcript Isoform Switching during Meiosis

(2018) Ze Cheng et al.   CELL

Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship

(2018) Marie A. Brunet et al.   GENOME RESEARCH

The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation

(2018) Maria Polycarpou-Schwarz et al.   ONCOGENE

Novel tumour suppressive protein encoded by circular RNA, circ-SHPRH, in glioblastomas

(2018) S Begum et al.   ONCOGENE

Mitoregulin: A lncRNA-Encoded Microprotein that Supports Mitochondrial Supercomplexes and Respiratory Efficiency

(2018) Colleen S. Stein et al.   Cell Reports

Translation of neutrally evolving peptides provides a basis for de novo gene evolution

(2018) Jorge Ruiz-Orera et al.   Nature Ecology & Evolution

MIEF1 Microprotein Regulates Mitochondrial Translation

(2018) Annie Rathore et al.   BIOCHEMISTRY

The Biogenesis, Functions, and Challenges of Circular RNAs

(2018) Xiang Li et al.   MOLECULAR CELL

Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration

(2018) Sonali Nashine et al.   Scientific Reports

A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma

(2018) Maolei Zhang et al.   Nature Communications

Non-AUG translation: a new start for protein synthesis in eukaryotes

(2017) Michael G. Kearse et al.   GENES & DEVELOPMENT

Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

(2017) Ivano Legnini et al.   MOLECULAR CELL

A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth

(2017) Jin-Zhou Huang et al.   MOLECULAR CELL

Small Proteins Encoded by Unannotated ORFs are Rising Stars of the Proteome, Confirming Shortcomings in Genome Annotations and Current Vision of an mRNA

(2017) Vivian Delcourt et al.   PROTEOMICS

Control of muscle formation by the fusogenic micropeptide myomixer

(2017) Pengpeng Bi et al.   SCIENCE

Mining for Micropeptides

(2017) Catherine A. Makarewich et al.   TRENDS IN CELL BIOLOGY

Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD

(2017) Xiaohua Yu et al.   Nature Communications

Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins

(2017) Sondos Samandi et al.   eLife

Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers

(2016) Laura J. Cobb et al.   Aging-US

mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide

(2016) Akinobu Matsumoto et al.   NATURE

A human microprotein that interacts with the mRNA decapping complex

(2016) Nadia G D'Lima et al.   Nature Chemical Biology

A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle

(2016) B. R. Nelson et al.   SCIENCE

Translation from the 5' untranslated region shapes the integrated stress response

(2016) S. R. Starck et al.   SCIENCE

Translational control by 5'-untranslated regions of eukaryotic mRNAs

(2016) A. G. Hinnebusch et al.   SCIENCE

MUC1-ARF—A Novel MUC1 Protein That Resides in the Nucleus and Is Expressed by Alternate Reading Frame Translation of MUC1 mRNA

(2016) Michael Chalick et al.   PLoS One

A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance

(2015) Douglas M. Anderson et al.   CELL

The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance

(2015) Changhan Lee et al.   Cell Metabolism

ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway

(2015) Lena Ho et al.   Cell Stem Cell

Expression of Human Hemojuvelin (HJV) Is Tightly Regulated by Two Upstream Open Reading Frames in HJV mRNA That Respond to Iron Overload in Hepatic Cells

(2015) Cláudia Onofre et al.   MOLECULAR AND CELLULAR BIOLOGY

A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation

(2015) Alexander P. Fields et al.   MOLECULAR CELL

Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18

(2015) Xingqian Zhang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Translation initiation mediated by RNA looping

(2015) Ki Young Paek et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18

(2015) Xingqian Zhang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Translation of 5′ leaders is pervasive in genes resistant to eIF2 repression

(2015) Dmitry E Andreev et al.   eLife

A Bicistronic MAVS Transcript Highlights a Class of Truncated Variants in Antiviral Immunity

(2014) Sky W. Brubaker et al.   CELL

Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation

(2014) A. A. Bazzini et al.   EMBO JOURNAL

A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining

(2014) Sarah A. Slavoff et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The role of FUS gene variants in neurodegenerative diseases

(2014) Hao Deng et al.   Nature Reviews Neurology

Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes

(2014) Nicholas T. Ingolia et al.   Cell Reports

The A2AAdenosine Receptor Is a Dual Coding Gene

(2013) Chien-fei Lee et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

An Out-of-frame Overlapping Reading Frame in the Ataxin-1 Coding Sequence Encodes a Novel Ataxin-1 Interacting Protein

(2013) Danny Bergeron et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Proto-genes and de novo gene birth

(2012) Anne-Ruxandra Carvunis et al.   NATURE

Peptidomic discovery of short open reading frame–encoded peptides in human cells

(2012) Sarah A Slavoff et al.   Nature Chemical Biology

Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals

(2012) Naresh C Bal et al.   NATURE MEDICINE

Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution

(2012) S. Lee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

An overlapping reading frame in the PRNP gene encodes a novel polypeptide distinct from the prion protein

(2011) Benoît Vanderperre et al.   FASEB JOURNAL

Phosphorylation of eIF2 Facilitates Ribosomal Bypass of an Inhibitory Upstream ORF to EnhanceCHOPTranslation

(2011) Lakshmi Reddy Palam et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

An additional ORF on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context

(2009) Yann Godet et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans

(2009) S. E. Calvo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

MELOE-1 is a new antigen overexpressed in melanomas and involved in adoptive T cell transfer efficiency

(2008) Yann Godet et al.   JOURNAL OF EXPERIMENTAL MEDICINE