bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023‒02‒12
four papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. Int J Mol Sci. 2023 Jan 20. pii: 2114. [Epub ahead of print]24(3):
      This review aims to consider retrospectively the available data on the coding properties of pri-microRNAs and the regulatory functions of their open reading frames (ORFs) and the encoded peptides (miPEPs). Studies identifying miPEPs and analyzing the fine molecular mechanisms of their functional activities are reviewed together with a brief description of the methods to identify pri-miRNA ORFs and the encoded protein products. Generally, miPEPs have been identified in many plant species of several families and in a few animal species. Importantly, molecular mechanisms of the miPEP action are often quite different between flowering plants and metazoan species. Requirement for the additional studies in these directions is highlighted by alternative findings concerning negative or positive regulation of pri-miRNA/miRNA expression by miPEPs in plants and animals. Additionally, the question of how miPEPs are distributed in non-flowering plant taxa is very important for understanding the evolutionary origin of such micropeptides. Evidently, further extensive studies are needed to explore the functions of miPEPs and the corresponding ORFs and to understand the full set of their roles in eukaryotic organisms. Thus, we address the most recent integrative views of different genomic, physiological, and molecular aspects concerning the expression of miPEPs and their possible fine functions.
    Keywords:  miPEP; microRNA; microRNA primary transcripts; micropeptide; short open reading frame; transcription of pri-miRNA; translation of microRNA primary transcripts
  2. Front Plant Sci. 2022 ;13 1051017
      In the past two decades, many plant peptides have been found to play crucial roles in various biological events by mediating cell-to-cell communications. However, a large number of small open reading frames (sORFs) or short genes capable of encoding peptides remain uncharacterized. In this study, we examined several candidate genes for peptides conserved between two model plants: Arabidopsis thaliana and Marchantia polymorpha. We examined their expression pattern in M. polymorpha and subcellular localization using a transient assay with Nicotiana benthamiana. We found that one candidate, MpSGF10B, was expressed in meristems, gemma cups, and male reproductive organs called antheridiophores. MpSGF10B has an N-terminal signal peptide followed by two leucine-rich repeat (LRR) domains and was secreted to the extracellular region in N. benthamiana and M. polymorpha. Compared with the wild type, two independent Mpsgf10b mutants had a slightly increased number of antheridiophores. It was revealed in gene ontology enrichment analysis that MpSGF10B was significantly co-expressed with genes related to cell cycle and development. These results suggest that MpSGF10B may be involved in the reproductive development of M. polymorpha. Our research should shed light on the unknown role of LRR-only proteins in land plants.
    Keywords:  LRR protein; Marchantia polymorpha; reproductive induction; signaling peptide; small ORF
  3. Front Endocrinol (Lausanne). 2023 ;14 1120533
      Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. The MOTS-c protein is transferred to the nucleus during metabolic stress and directs the expression of nuclear genes to promote cell balance. Different tissues co-expressed the protein with mitochondria, and plasma also contained the protein, but its level decreased with age. In addition, MOTS-c has been shown to improve glucose metabolism in skeletal muscle, which indicates its benefits for diseases such as diabetes, obesity, and aging. Nevertheless, MOTS-c has been used less frequently in disease treatment, and no effective method of applying MOTS-c in the clinic has been developed. Throughout this paper, we discussed the discovery and physiological function of mitochondrial-derived polypeptide MOTS-c, and the application of MOTS-c in the treatment of various diseases, such as aging, cardiovascular disease, insulin resistance, and inflammation. To provide additional ideas for future research and development, we tapped into the molecular mechanisms and therapeutic potentials of MOTS-c to improve diseases and combined the technology with synthetic biology in order to offer a new approach to its development and application.
    Keywords:  MOTS-c; endocrine; mitochondrial-derived peptide; synthetic biology; therapeutic exploitation
  4. Microbiology (Reading). 2022 Nov;168(11):
      Bacterial genomes harbour cryptic prophages that are mostly transcriptionally silent with many unannotated genes. Still, cryptic prophages may contribute to their host fitness and phenotypes. In Bacillus subtilis, the yqaF-yqaN operon belongs to the prophage element skin, and is tightly repressed by the Xre-like repressor SknR. This operon contains several small ORFs (smORFs) potentially encoding small-sized proteins. The smORF-encoded peptide YqaH was previously reported to bind to the replication initiator DnaA. Here, using a yeast two-hybrid assay, we found that YqaH binds to the DNA binding domain IV of DnaA and interacts with Spo0A, a master regulator of sporulation. We isolated single amino acid substitutions in YqaH that abolished the interaction with DnaA but not with Spo0A. Then, using a plasmid-based inducible system to overexpress yqaH WT and mutant derivatives, we studied in B. subtilis the phenotypes associated with the specific loss-of-interaction with DnaA (DnaA_LOI). We found that expression of yqaH carrying DnaA_LOI mutations abolished the deleterious effects of yqaH WT expression on chromosome segregation, replication initiation and DnaA-regulated transcription. When YqaH was induced after vegetative growth, DnaA_LOI mutations abolished the drastic effects of YqaH WT on sporulation and biofilm formation. Thus, YqaH inhibits replication, sporulation and biofilm formation mainly by antagonizing DnaA in a manner that is independent of the cell cycle checkpoint Sda.
    Keywords:  Bacillus subtilis; DnaA; SEP; Spo0A; skin element; small ORF