bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2026–04–12
seven papers selected by
Thomas Farid Martínez, University of California, Irvine



  1. Commun Biol. 2026 Apr 04.
      Plants can adapt to environmental change through a variety of transcriptional and translational mechanisms. Although extensive knowledge exists about plant stress responses at the transcriptional level, understanding of these responses at the translational level is limited. This study aimed to evaluate the translational dynamics of plants in a simulated microgravity environment through the utilization of a ribosome profiling assay. A comparative analysis of ribosome profiling data and RNA-seq on a global scale demonstrated a modest correlation in the alteration of gene expression between transcriptional and translational levels. However, under one third of responsive genes exhibited concurrent transcriptional and translational activities. We found that simulated microgravity simulation elicited separate transcriptional and translational responses in plants. The findings indicated a significant alteration in the translational efficiency (TE) of 1081 genes under simulated microgravity conditions. Subsequent analysis identified specific sequence characteristics, including GC content and coding sequence length, as influential factors on gene TE. The abundance of upstream open reading frames (uORFs) within gene promoters indicates a possible influence on the translation efficiency of primary open reading frames located downstream. These results suggested that in response to simulated microgravity, plants had a responsive translational mechanism that interacted with transcription in a coordinated manner.
    DOI:  https://doi.org/10.1038/s42003-026-09991-3
  2. Br J Cancer. 2026 Apr 06.
       BACKGROUND AND PURPOSE: Lung adenocarcinoma (LUAD) has limited therapeutic targets and poor survival. Noncanonical open reading frames (ORFs) in long noncoding RNAs (lncRNAs) may encode functional microproteins, but their roles in LUAD remain unclear. This study aims to characterise the LINC00973-encoded microprotein L3EMP and to investigate its tumour-promoting mechanisms and therapeutic potential.
    METHODS: L3EMP was identified through ribosome profiling and RNA sequencing, with its expression confirmed by mass spectrometry (MS) and Western blotting. Its functional relevance was further validated using CRISPR/Cas9-mediated gene manipulation. Functional experiments were performed in LUAD cells and chimeric antigen receptor T (CAR-T) cell models to elucidate the underlying molecular mechanisms. The interaction between USP22 and SIRT1 was investigated via ubiquitination assays and signalling pathway profiling. Finally, immunotherapeutic potential was evaluated using synthetic L3EMP peptides and B7-H3-targeted CAR-T cells.
    KEY RESULTS: (1) L3EMP, a microprotein encoded by LINC00973, is overexpressed in LUAD and its expression level is correlated with poor prognosis. (2) L3EMP stabilises SIRT1 by promoting USP22-mediated deubiquitination. This forms a positive feedback loop involving YY1 that activates AKT/ERK signalling, thereby promoting proliferation and invasion. (3) L3EMP knockout suppresses tumour growth in PDX models. (4) Synthetic L3EMP peptide enhances antitumor immunity as a neoantigen. (5) L3EMP deletion synergises with B7-H3 CAR-T therapy via IFN-γ pathway activation.
    CONCLUSIONS AND IMPLICATIONS: L3EMP contributes to LUAD progression through the USP22/SIRT1 signalling axis and represents both a therapeutic target and an immunogenic neoantigen. Targeting L3EMP or its pathway inhibits tumour growth, while the synthetic L3EMP peptide can potentiate immunotherapy. The combination of L3EMP depletion and B7-H3 CAR-T therapy enhances antitumor efficacy, suggesting a promising combinatorial strategy for LUAD treatment.
    DOI:  https://doi.org/10.1038/s41416-026-03387-0
  3. Physiol Plant. 2026 Mar-Apr;178(2):178(2): e70860
      Phloem sap proteomic studies have previously revealed that phloem sap composition varies during development and upon floral induction. Specific proteins, lipids, messenger RNAs (mRNAs), and peptides have been shown to accumulate at different developmental stages. Peptides are of special interest since they have the potential to act as regulatory molecules controlling plant responses to environmental changes, such as salinity and water stress, plant-microbe interactions, and developmental changes. In this context, we have characterized Arabidopsis thaliana phloem exudates to identify proteins and peptides with the potential to control flowering time, acting as signals fine-tuning plant development. In this work, we present the proteomic profiles of the phloem sap samples during floral transition along with the identification of proteins and peptides that showed changes in abundance during floral transition, suggesting that they could potentially have a role in the control of flowering. Among those, we have described the abundance pattern of the sORF1511 peptide in the phloem sap, which varies upon floral induction. We show that sORF1511 overexpression affects bolting time and alters the expression of several genes involved in the control of flowering time.
    Keywords:  flowering time; peptides; phloem proteomics; small open reading frames
    DOI:  https://doi.org/10.1111/ppl.70860
  4. Curr Opin Virol. 2026 Apr 08. pii: S1879-6257(26)00019-2. [Epub ahead of print]76 101527
      Orthoflaviviruses, a genus of RNA viruses transmitted primarily by arthropods, exhibit remarkable adaptability, infecting a broad range of hosts, from insects to vertebrates, despite their compact ∼11-kilobase genome. To maximize their functional repertoire and modulate host interactions, they employ a variety of canonical and noncanonical expression mechanisms. Here, we discuss how orthoflaviviruses utilize noncoding RNAs, including subgenomic flavivirus RNAs and viral microRNAs, as well as unconventional translational strategies, such as upstream open reading frames and programmed ribosomal frameshifting, to enhance viral replication, evade immune responses, and adapt to diverse hosts. These noncanonical genome optimization strategies highlight the evolutionary plasticity of orthoflaviviruses, enabling them to manipulate the cellular machinery of phylogenetically distant hosts. Understanding these mechanisms not only advances our knowledge of the biology of these emerging and re-emerging viruses but also provides insights for developing antiviral therapies and vaccine strategies.
    DOI:  https://doi.org/10.1016/j.coviro.2026.101527
  5. Cell Commun Signal. 2026 Apr 06.
      
    Keywords:  Mito-nuclear crosstalk; Mitochondria; Mitochondrial DNA; Mitochondrial-derived Peptides; Mitochondrial-derived non-coding RNAs; Retrograde signalling
    DOI:  https://doi.org/10.1186/s12964-026-02858-4
  6. Cell Mol Life Sci. 2026 Apr 10.
      
    Keywords:  Biomarker; Cancer hallmarks; Long non-coding RNA (lncRNA); Micropeptide; Targeted therapy; Tumorigenesis
    DOI:  https://doi.org/10.1007/s00018-026-06151-y
  7. Nat Commun. 2026 Apr 04.
      Mitochondrial translation is essential for cellular function, and its dysregulation is associated with mitochondrial disorders and cancer. However, the mechanisms by which human mitochondrial ribosomes initiate translation remain poorly understood, particularly because mitochondrial mRNAs generally lack the 5' untranslated regions that guide translation initiation in bacterial and cytoplasmic systems. Using real-time single-molecule fluorescence measurements, biochemical assays, and cryo-EM analysis, we show that human mitochondrial translation initiation occurs through two parallel pathways. In one pathway, leaderless mRNA first loads onto the 28S small subunit, followed by recruitment of the 39S large subunit to form the 55S initiation complex. In the second pathway, a preassembled 55S monosome directly loads onto leaderless mRNA. Both pathways require recruitment of mtIF2 and fMet-tRNAMet before mRNA binding. However, the monosome-loading pathway tolerates non-formylated Met-tRNAMet and is suppressed by mtIF3. Together, these findings define the heterogeneous pathways of human mitochondrial translation initiation on leaderless mRNAs.
    DOI:  https://doi.org/10.1038/s41467-026-71535-4