bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2021‒04‒04
two papers selected by
Thomas Martinez
Salk Institute for Biological Studies

  1. Int J Mol Sci. 2021 Mar 26. pii: 3432. [Epub ahead of print]22(7):
      Some miRNAs are located in RNA precursors (pri-miRNAs) annotated as long non-coding (lncRNAs) due to absence of long open reading frames (ORFs). However, recent studies have shown that some lnc pri-miRNAs encode peptides called miPEPs (miRNA-encoded peptides). Initially discovered in plants, three miPEPs have also been identified in humans. Herein, we found that a dozen human pri-miRNAs potentially encode miPEPs, as revealed by ribosome profiling and proteomic databases survey. So far, the only known function of plant miPEPs is to enhance the transcription of their own pri-miRNAs, thereby increasing the level and activity of their associated miRNAs and downregulating the expression of their target genes. To date, in humans, only miPEP133 was shown to promote a positive autoregulatory loop. We investigated whether other human miPEPs are also involved in regulating the expression of their miRNAs by studying miPEP155, encoded by the lnc MIR155HG, miPEP497, a sORF-encoded peptide within lnc MIR497HG, and miPEP200a, encoded by the pri-miRNA of miR-200a/miR-200b. We show that overexpression of these miPEPs is unable to impact the expression/activity of their own pri-miRNA/miRNAs in humans, indicating that the positive feedback regulation observed with plant miPEPs and human miPEP133 is not a general rule of human miPEP function.
    Keywords:  miPEP; miRNA; micropeptides; pri-miRNA; short ORFs
  2. FEBS J. 2021 Mar 29.
      The large abundance of small open reading frames (smORFs) in prokaryotic and eukaryotic genomes and the plethora of smORF-encoded small proteins became only apparent with the constant advancements in bioinformatics, genomic, proteomic and biochemical tools. Small proteins are typically defined as proteins of less than 50 amino acids in prokaryotes and of less than 100 amino acids in eukaryotes and their importance for cell physiology and cellular adaptation is only beginning to emerge. In contrast to antimicrobial peptides, which are secreted by prokaryotic and eukaryotic cells for combatting pathogens and competitors, small proteins act within the producing cell mainly by stabilizing protein assemblies and by modifying the activity of larger proteins. Production of small proteins is frequently linked to stress conditions or environmental changes and therefore cells seem to use small proteins as intracellular modifiers for adjusting cell metabolism to different intra- and extracellular cues. However, the size of small proteins imposes a major challenge for the cellular machinery required for protein folding and intracellular trafficking and recent data indicate that small proteins can engage distinct trafficking pathways. In the current review, we describe the diversity of small proteins in prokaryotes and eukaryotes, highlight distinct and common features and illustrate how they are handled by the protein trafficking machineries in prokaryotic and eukaryotic cells. Finally, we also discuss future topics of research on this fascinating but largely unexplored group of proteins.
    Keywords:  Sec61 complex; SecYEG translocon; Small membrane proteins; YidC; antimicrobial peptides; cytochrome oxidase; mRNA targeting; protein targeting; stress response