bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2021‒01‒03
three papers selected by
Thomas Martinez
Salk Institute for Biological Studies

  1. J Biochem. 2021 Jan 02. pii: mvaa143. [Epub ahead of print]
      Whole transcriptome analyses have revealed that mammalian genomes are massively transcribed, resulting in the production of huge numbers of transcripts with unknown functions (TUFs). Previous research has categorized most TUFs as noncoding RNAs (ncRNAs) because most previously studied TUFs do not encode open reading frames (ORFs) with biologically significant lengths (>100 amino acids). Recent studies, however, have reported that several transcripts harboring small ORFs (sORFs) that encode peptides shorter than 100 amino acids are translated and play important biological functions. Here, we examined the translational capacity of transcripts annotated as ncRNAs in human cells, and identified several hundreds of ribosome-associated transcripts previously annotated as ncRNAs. Ribosome footprinting and polysome profiling analyses revealed that 61 of them are potentially translatable. Among them, 45 were non-nonsense-mediated mRNA decay targets, suggesting that they are productive mRNAs. We confirmed the translation of one ncRNA, LINC00493, by luciferase reporter assaying and western blotting of a FLAG-tagged LINC00493 peptide. While proteomic analysis revealed that the LINC00493 peptide interacts with many mitochondrial proteins, immunofluorescence assays showed that its peptide is mitochondrially localized. Our findings indicate that some transcripts annotated as ncRNAs encode peptides and that unannotated peptides may perform important roles in cells.
    Keywords:  TUFs; ncRNAs; ribosomes; sORFs; short peptides
  2. Microorganisms. 2020 Dec 19. pii: E2036. [Epub ahead of print]8(12):
      Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics have led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) are not represented in the conventional protein databases and this "ghost proteome" was not considered until recently. Some of these proteins are functional and there is growing evidence that they are involved in central functions in physiological and physiopathological context. Based on our experience with AltProts, we were interested in finding out their interaction with the viral protein coming from the SARS-CoV-2 virus, responsible for the 2020 COVID-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by affinity purification in co-immunoprecipitation (co-IP) in the perspective of drug repurposing. The initial work revealed the interaction between 332 human cellular reference proteins (RefProts) with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study), plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the ghost proteome for discovering new therapeutic targets, and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.
    Keywords:  Alternative ORF; Alternative protein; OpenProt; SARS-Cov-2; anti-viral response; drug repurposing; ghost protein; innate immune response; interactomics; non-coding RNA
  3. Trends Plant Sci. 2020 Dec 19. pii: S1360-1385(20)30381-2. [Epub ahead of print]
      Some pri-miRNAs can code for short peptides called micropeptides (miPEPs) and it has been suggested that these peptides positively regulate the accumulation of their associated miRNAs. Recent data further support this model and point towards the potential for miPEPs to be used in the agricultural sector to improve crop agronomic traits.
    Keywords:  miPEPs; miRNA; regulatory peptides