bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2021‒03‒21
three papers selected by
Thomas Martinez
Salk Institute for Biological Studies

  1. Front Plant Sci. 2021 ;12 641351
      Peptides composed of a short chain of amino acids can play significant roles in plant growth, development, and stress responses. Most of these functional peptides are derived by either processing precursor proteins or direct translation of small open reading frames present in the genome and sometimes located in the untranslated region sequence of a messenger RNA. Generally, canonical peptides serve as local signal molecules mediating short- or long-distance intercellular communication. Also, they are commonly used as ligands perceived by an associated receptor, triggering cellular signaling transduction. In recent years, increasing pieces of evidence from studies in both plants and animals have revealed that peptides are also encoded by RNAs currently defined as non-coding RNAs (ncRNAs), including long ncRNAs, circular RNAs, and primary microRNAs. Primary microRNAs (miRNAs) have been reported to encode regulatory peptides in Arabidopsis, grapevine, soybean, and Medicago, called miRNA-encoded peptides (miPEPs). Remarkably, overexpression or exogenous applications of miPEPs specifically increase the expression level of their corresponding miRNAs by enhancing the transcription of the MIRNA (MIR) genes. Here, we first outline the current knowledge regarding the coding of putative ncRNAs. Notably, we review in detail the limited studies available regarding the translation of miPEPs and their relevant regulatory mechanisms. Furthermore, we discuss the potential cellular and molecular mechanisms in which miPEPs might be involved in plants and raise problems that needed to be solved.
    Keywords:  miPEP; miRNA; miRNA-encoded peptide; non-coding RNA; peptides; pri-miRNA
  2. PLoS One. 2021 ;16(3): e0248634
      Glioma is a lethal malignant brain cancer, and many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating tumor proliferation, migration, apoptosis, and differentiation. Recently, new studies have suggested that some long noncoding RNAs containing small open reading frames can encode small peptides and form oligomers for water or ion regulation. However, because the peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatics methods to identify and evaluate lncRNAs, which may encode small transmembrane peptides in gliomas. Combining ab initio homology modeling, molecular dynamics simulations, and free energy calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs. We found that one key hub lncRNA, namely, DLEU1, which contains two smORFs (ORF1 and ORF8), encodes small peptides that form pentameric channels. The mechanics of water and ion (Na+ and Cl-) transport through this pentameric channel were simulated. The potential mean force of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 permeated neither ions nor water. This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, this study provides a theoretical basis for drug development.
  3. Biochim Biophys Acta Mol Basis Dis. 2021 Mar 12. pii: S0925-4439(21)00059-4. [Epub ahead of print] 166126
      Mitochondrial-derived peptide (MOTS-c) has gained increasing attention as a promising therapeutic or prevention strategy for obesity and diabetes mellitus. MOTS-c targets the folate cycle, leading to an accumulation of 5-aminomidazole-4-carboxamide ribonucleotide (AICAR) as well as AMPK activation. AMPK is a well-known upstream regulator of the proliferation-activated receptor co-activator 1 (PGC-1α), which can improve mitochondrial biogenesis via co-transcriptional modifications. We hypothesized that AMPK can induce the expression of MOTS-c through PGC-1α. Our study aimed to explore whether MOTS-c and/or exercise can regulate MOTS-c expression, attenuate insulin resistance and enhance glucose metabolism both in vitro and in vivo. It was found that C2C12 myotubes exposed to Compound C (an AMPK inhibitor) had deceases in the protein and mRNA expressions of PGC-1α and MOTS-c. PGC-1α knockdown downregulated the protein and mRNA expressions of MOTS-c in C2C12 myotubes, whereas both PGC-1α overexpression and recombinant MOTS-c supplementation upregulated the protein and mRNA expressions of MOTS-c in C2C12 myotubes. Furthermore, the skeletal muscle and plasma levels of MOTS-c were markedly reduced in high-fat diet-induced obese mice. Treadmill training remarkably upregulated the protein levels of MOTS-c, PGC-1α and GLUT4, along with the phosphorylation levels of AMPK and ACC. Altogether, these results indicate that AMPK/PGC-1α pathway can mediate the secretion and/or production of MOTS-c in skeletal muscle, implying the possible roles of exercise intervention and recombinant MOTS-c in treating obesity and diabetes mellitus.
    Keywords:  AMPK; Exercise; Insulin resistance; MOTS-c; PGC-1α; Skeletal muscle