bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2024‒02‒04
three papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction.
  2. CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.
  3. Translatome and Transcriptome Analyses Reveal the Mechanism that Underlies the Enhancement of Salt Stress by the Small Peptide Ospep5 in Plants.
  1. EMBO Rep. 2024 Jan 30.
    A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction.
    Sibei Tang, Junxun Zhang, Fangzhou Lou, Hong Zhou, Xiaojie Cai, Zhikai Wang, Libo Sun, Yang Sun, Xiangxiao Li, Li Fan, Yan Li, Xinping Jin, Siyu Deng, Qianqian Yin, Jing Bai, Hong Wang, Honglin Wang.
      Micropeptides encoded by short open reading frames (sORFs) within long noncoding RNAs (lncRNAs) are beginning to be discovered and characterized as regulators of biological and pathological processes. Here, we find that lncRNA Dleu2 encodes a 17-amino-acid micropeptide, which we name Dleu2-17aa, that is abundantly expressed in T cells. Dleu2-17aa promotes inducible regulatory T (iTreg) cell generation by interacting with SMAD Family Member 3 (Smad3) and enhancing its binding to the Foxp3 conserved non-coding DNA sequence 1 (CNS1) region. Importantly, the genetic deletion of Dleu2-17aa in mice by start codon mutation impairs iTreg generation and worsens experimental autoimmune encephalomyelitis (EAE). Conversely, the exogenous supplementation of Dleu2-17aa relieves EAE. Our findings demonstrate an indispensable role of Dleu2-17aa in maintaining immune homeostasis and suggest therapeutic applications for this peptide in treating autoimmune diseases.
    Keywords:  Autoimmunity; Dleu2; LncRNA Encoded Micropeptide; Smad3; Treg Cell
    DOI:  https://doi.org/10.1038/s44319-024-00070-4
  2. Mol Cell. 2024 Jan 30. pii: S1097-2765(24)00007-8. [Epub ahead of print]
    CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.
    Rachel Anderson, Michael R Das, Yeonji Chang, Kelsey Farenhem, Cameron O Schmitz, Ankur Jain.
      Expansions of CAG trinucleotide repeats cause several rare neurodegenerative diseases. The disease-causing repeats are translated in multiple reading frames and without an identifiable initiation codon. The molecular mechanism of this repeat-associated non-AUG (RAN) translation is not known. We find that expanded CAG repeats create new splice acceptor sites. Splicing of proximal donors to the repeats produces unexpected repeat-containing transcripts. Upon splicing, depending on the sequences surrounding the donor, CAG repeats may become embedded in AUG-initiated open reading frames. Canonical AUG-initiated translation of these aberrant RNAs may account for proteins that have been attributed to RAN translation. Disruption of the relevant splice donors or the in-frame AUG initiation codons is sufficient to abrogate RAN translation. Our findings provide a molecular explanation for the abnormal translation products observed in CAG trinucleotide repeat expansion disorders and add to the repertoire of mechanisms by which repeat expansion mutations disrupt cellular functions.
    Keywords:  Huntington's disease; RAN translation; RNA splicing; polyglutamine diseases; repeat expansion disorders; repeat-associated non-AUG translation; spinocerebellar ataxia
    DOI:  https://doi.org/10.1016/j.molcel.2024.01.006
  3. J Agric Food Chem. 2024 Jan 30.
    Translatome and Transcriptome Analyses Reveal the Mechanism that Underlies the Enhancement of Salt Stress by the Small Peptide Ospep5 in Plants.
    Jinyan Wang, Yang Li, Mingyue Li, Wenting Zhang, Yaping Lu, Kai Hua, Xitie Ling, Tianzi Chen, Dongshu Guo, Yuwen Yang, Zhongbing Zheng, Qing Liu, Baolong Zhang.
      Salt stress significantly impedes plant growth and the crop yield. This study utilized de novo transcriptome assembly and ribosome profiling to explore mRNA translation's role in rice salt tolerance. We identified unrecognized translated open reading frames (ORFs), including 42 upstream transcripts and 86 unannotated transcripts. A noteworthy discovery was the role of a small ORF, Ospep5, in conferring salt tolerance. Overexpression of Ospep5 in plants increased salt tolerance, while its absence led to heightened sensitivity. This hypothesis was corroborated by the findings that exogenous application of the synthetic small peptide Ospep5 bolstered salt tolerance in both rice and Arabidopsis. We found that the mechanism underpinning the Ospep5-mediated salt tolerance involves the maintenance of intracellular Na+/K+ homeostasis, facilitated by upregulation of high-affinity potassium transporters (HKT) and Na+/H+ exchangers (SOS1). Furthermore, a comprehensive multiomics approach, particularly ribosome profiling, is instrumental in uncovering unannotated ORFs and elucidating their functions in plant stress responses.
    Keywords:  peptidome; rice salt tolerance; small peptides; transcriptome; translatome
    DOI:  https://doi.org/10.1021/acs.jafc.3c08528
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