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Related Experiment Videos

A hidden human proteome encoded by 'non-coding' genes.

Shaohua Lu1, Jing Zhang1, Xinlei Lian1,2

  • 1Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

Nucleic Acids Research
|July 25, 2019
PubMed
Summary
This summary is machine-generated.

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Scientists discovered a hidden human proteome encoded by long non-coding RNAs (lncRNAs). This research reveals novel proteins, expanding our understanding of the human genome and its functional capabilities.

Area of Science:

  • Genomics
  • Proteomics
  • Molecular Biology

Background:

  • The 98% of the human genome annotated as 'non-coding' has been debated for its potential to encode functional proteins beyond short peptides.
  • Advancements in sequencing and profiling technologies are crucial for exploring the functional potential of non-coding genomic regions.

Purpose of the Study:

  • To investigate the potential of long non-coding RNAs (lncRNAs) to encode functional proteins.
  • To identify and characterize novel proteins originating from lncRNAs.
  • To explore the evolutionary origins and functional roles of these newly discovered proteins.

Main Methods:

  • Full-length translating mRNA sequencing and ribosome profiling to identify actively translated lncRNAs.
  • Shotgun proteomics and multiple reaction monitoring (MRM)/parallel reaction monitoring (PRM) for detecting and verifying lncRNA-encoded peptides and proteins.

Related Experiment Videos

  • Immunoblotting, assays for translation efficiency, RNA folding, and intracellular localization studies to characterize protein function.
  • Functional assays, including cell proliferation studies for specific proteins like UBAP1-AST6.

    • Main Results:

    • Identified 3330 long non-coding RNAs (lncRNAs) bound to ribosomes with active translation elongation.
    • Detected 308 novel proteins encoded by lncRNAs, with 207 unique peptides verified by MRM/PRM and 10 proteins confirmed by immunoblotting.
    • Characterized these new proteins as having distinct physical and chemical properties compared to canonical proteins, with evidence of recent evolutionary emergence primarily in primates.
    • Verified the nucleolar localization and preferential expression of UBAP1-AST6 in lung cancer cell lines, demonstrating its role in cell proliferation.

    Conclusions:

    • Experimentally confirmed a hidden human proteome encoded by lncRNAs, significantly expanding the known human protein-coding capacity.
    • These findings provide a valuable resource for annotating new human proteins and understanding the functional significance of the non-coding genome.
    • The discovery of lncRNA-encoded proteins, particularly UBAP1-AST6's role in cancer cell proliferation, opens new avenues for research in molecular biology and disease mechanisms.