ArticleNature structural & molecular biology2023
CRISPR-Cas9-based functional interrogation of unconventional translatome reveals human cancer dependency on cryptic non-canonical open reading frames.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- Ribo-ITP enables identification of translons from limited input samples.Nature communications · 2026Article
- N7-Methylguanosine Modification in Colorectal Cancer: Molecular Insights and Clinical Implications.International journal of molecular sciences · 2026Review
- An Artificial Antibody-Based Toolbox Accelerates Validation of Hidden Microproteins Encoded by the Dark Genome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- Bright side of the dark genome: antigens for next-gen cancer vaccines.Journal for immunotherapy of cancer · 2026Review
- Review
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 2026Article
- The lncRNA GAS5-encoded micropeptide facilitates influenza virus replication through modulation of the Wnt/β-catenin signaling pathway.Current research in microbial sciences · 2026Article
- The 'non-conventional' peptidome: A new layer in plant regulatory mechanisms.Plant communications · 2025Review
- Decoding the Cryptic Proteome Between Antigens and Novel Functional Proteins.European journal of immunology · 2025Review
- A large-scale sORF screen identifies putative microproteins involved in cancer cell fitness.iScience · 2025Article
- Microproteins in cancer: identification, biological functions, and clinical implications.Trends in genetics : TIG · 2025Review
- Finding functional microproteins.Trends in genetics : TIG · 2025Review
- The cryptic lncRNA-encoded microprotein TPM3P9 drives oncogenic RNA splicing and tumorigenesis.Signal transduction and targeted therapy · 2025Article
- Comparative Transcriptomic Analysis Provides Insight into Spatiotemporal Expression Patterns of Pivotal Genes During Critical Growth Stages in Min Pig Breed.Biomolecules · 2025Article
- Review
- Microproteins unveiling new dimensions in cancer.Functional & integrative genomics · 2024Review
- Multi-Omics Mining of lncRNAs with Biological and Clinical Relevance in Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
Abstract
Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR-Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a primate-specific, long noncoding RNA, the expression of which is associated with poor prognosis in CRC, is low in normal tissues and is specifically elevated in CRC and several other cancer types. Mechanistically, SMIMP interacts with the ATPase-forming domains of SMC1A, the core subunit of the cohesin complex, and facilitates SMC1A binding to cis-regulatory elements to promote epigenetic repression of the tumor-suppressive cell cycle regulators encoded by CDKN1A and CDKN2B. Thus, our study reveals a cryptic microprotein as an important component of cohesin-mediated gene regulation and suggests that the 'dark' proteome, encoded by cryptic non-canonical ORFs, may contain potential therapeutic or diagnostic targets.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.