
February 2nd, 2025
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers:
- Xu et al. developed HMPA, which uncovers hidden peptides from noncoding regions using ribosome profiling and mass spectrometry, revealing roles in cell signaling and disease.
- LncPepAtlas, a database by Zhou et al. maps peptides encoded by long non-coding RNAs, highlighting their translational potential and functional significance.
- A study by Pai et al. examines microprotein regulation under pro-inflammatory and pro-fibrotic stimuli, uncovering dynamic translation of microproteins linked to immune responses and fibrosis.
Together, these works reveal the hidden complexity of the proteome, offering new insights into biomarkers and therapeutic targets.
HMPA: a pioneering framework for the noncanonical peptidome from discovery to functional insights
Briefings in Bioinformatics, 2024
Su X., Shi C., Liu F., TanM., Wang Y., Zhu L., Chen Y., Yu M., Wang X., Liu J., Liu Y., Lin W., Fang Z., Sun Q., Zhou T., Lin A.
The paper introduces the Hybrid Multi-layered Peptidomic Approach (HMPA), a groundbreaking framework designed to systematically identify and characterize the noncanonical peptidome. These peptides, derived from noncoding regions, alternative open reading frames (ORFs), and cryptic translation events, have remained largely unexplored in conventional proteomics. By integrating advanced computational tools, ribosome profiling, and mass spectrometry, HMPA addresses this knowledge gap, offering a comprehensive pipeline for uncovering and validating hidden peptides and linking them to biological functions.
Ribosome profiling (Ribo-seq) is central to HMPA, providing high-resolution data on active translation events across the genome. This technique identifies ribosome-protected mRNA fragments, pinpointing regions of translation, including small ORFs, upstream initiation sites, and noncoding regions. The study demonstrates that ribosome profiling reveals pervasive translation activity outside annotated coding regions, challenging traditional genome annotations. These noncanonical peptides are shown to play roles in immune modulation, intracellular signalling, and potentially disease pathogenesis, significantly broadening the scope of known functional peptides.
HMPA aims to establish a new paradigm in proteomics, enabling the discovery of previously hidden peptide biomarkers and therapeutic targets. By systematically uncovering and characterizing the noncanonical peptidome, this framework enhances our understanding of the proteome’s complexity, offering novel insights into cellular mechanisms and disease processes. HMPA lays the foundation for leveraging these insights in precision medicine and drug development, addressing critical gaps in translational research.
Learn more about EIRNA Bio’s ribosome profiling service here.
LncPepAtlas: a comprehensive resource for exploring the translational landscape of long non-coding RNAs
Nucleic Acids Research, 2024
Zhou X., Qin Y., Li J., Fan L., Zhang S., Zhang B., Wu L., Gao A., Yang Y., Lv X., Guo B., Sun L.
The paper introduces LncPepAtlas, an innovative database designed to systematically catalog and explore the translational landscape of long non-coding RNAs (lncRNAs). Traditionally viewed as transcriptional regulators, lncRNAs have recently been shown to encode functional peptides, highlighting their underappreciated role in proteomics. LncPepAtlas bridges a critical gap by integrating advanced bioinformatics, experimental data, and predictive tools to uncover the hidden coding potential of lncRNAs.
LncPepAtlas identifies thousands of putative peptides encoded by lncRNAs, providing evidence of widespread translation in regions previously deemed noncoding. The database integrates mass spectrometry data, ribosome profiling, and sequence-based analyses to systematically annotate these peptides. Notably, many identified lncRNA-derived peptides exhibit conserved sequences, suggesting functional significance, particularly in cellular signaling and disease-related pathways.
Ribosome profiling (Ribo-seq) was employed to identify active translation sites across lncRNAs. By capturing ribosome-protected mRNA fragments, the authors pinpointed regions of active peptide synthesis, revealing extensive translational activity in lncRNA regions. These findings challenge the traditional dichotomy between coding and noncoding RNA, emphasizing lncRNAs as a reservoir of bioactive peptides.
LncPepAtlas provides a comprehensive resource for understanding the translational potential of lncRNAs and their functional roles. By uncovering novel peptide candidates, it opens new avenues for biomarker discovery and therapeutic development, advancing our understanding of the noncanonical proteome and its impact on health and disease.
Learn more about EIRNA Bio’s ribosome profiling service here.
Microprotein-encoding RNA regulation in cells treated with pro-inflammatory and pro-fibrotic stimuli
BMC Genomics, 2024
Pai V. J., Lau C. J., Garcia-Ruiz A., Donaldson C., Vaughan J. M., Miller B., De Souza E. V., Pinto A. M., Diedrich J., Gavva N. R., Yu S., DeBoever C., Horman S. R. and Saghatelian A.
This study investigates the regulation of microprotein-encoding RNAs in response to pro-inflammatory and pro-fibrotic stimuli, shedding light on the role of small peptides encoded by previously unannotated open reading frames (ORFs). These microproteins, often overlooked in conventional proteomics, are emerging as critical players in cellular stress responses and disease processes such as fibrosis and inflammation.
Key findings demonstrate that treatment with pro-inflammatory (e.g., TNF-α) and pro-fibrotic (e.g., TGF-β) stimuli induces widespread changes in the expression and translation of microprotein-encoding RNAs. Using an integrative approach, the study identifies numerous microproteins linked to immune regulation, extracellular matrix remodelling, and cellular signalling. Importantly, several of these microproteins are differentially expressed in disease-relevant contexts, highlighting their potential as biomarkers or therapeutic targets.
Ribosome profiling provides a methodology to capture active translation across the transcriptome, pinpointing regions where microproteins are synthesized. The analysis uncovers extensive translation in small ORFs, many of which were previously classified as noncoding. This approach reveals the dynamic regulation of microprotein synthesis in response to inflammatory and fibrotic signals, offering critical insights into their functional roles.
By unveiling the translational regulation of microproteins during cellular stress, this study expands our understanding of the noncanonical proteome’s role in disease mechanisms. These findings pave the way for novel therapeutic strategies targeting microproteins to combat inflammation and fibrosis.
Learn more about EIRNA Bio’s ribosome profiling service here.