bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023–01–22
three papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Rise of bacterial small proteins and peptides in therapeutic applications.
  2. Systematic identification of smORFs in domestic silkworm (Bombyx mori).
  3. Annotation of uORFs in the OMIM genes allows to reveal pathogenic variants in 5'UTRs.
  1. Protein Pept Lett. 2023 Jan 18.
    Rise of bacterial small proteins and peptides in therapeutic applications.
    Ruby Shelin, Shanmugaraja Meenakshi.
       BACKGROUND: Polypeptides that comprise less than 100 amino acids (50 amino acids in some cases) are referred to as small proteins (SPs), however, as of date, there is no strict definition. In contrast to the small polypeptides that arise due to proteolytic activity or abrupt protein synthesis, SPs are coded by small open reading frames (sORFs) and are conventionally synthesized by ribosomes.
    PURPOSE OF THE REVIEW: Although proteins that contain more than 100 amino acids have been studied exquisitely, studies on small proteins have been largely ignored, basically due to unsuccessful detection of these SPs by traditional methodologies/techniques. Serendipitous observation of several small proteins and elucidation of their vital functions in cellular processes opened the floodgate of a new area of research on the new family of proteins, "Small proteins". Having known the significance of such SPs, several advanced techniques are being developed to precisely identify and characterize them.
    CONCLUSION: Bacterial small proteins (BSPs) are being intensely investigated in recent days and that has brought the versatile role of BSPs into the limelight. In particular, identification of the fact that BSPs exhibit antimicrobial activity has further expanded its scope in the area of therapeutics. Since the microbiome plays an inevitable role in determining the outcome of personalized medicine, studies on the secretory small proteins of the microbiome are gaining momentum. This review discusses the importance of bacterial small proteins and peptides in terms of their therapeutic applications.
    Keywords:  Bacterial small proteins; Peptides of the human microbiome; Small open reading frame; Therapeutic application of bacterial small
    DOI:  https://doi.org/10.2174/0929866530666230118144723
  2. PeerJ. 2023 ;11 e14682
    Systematic identification of smORFs in domestic silkworm (Bombyx mori).
    Linrong Wan, Wenfu Xiao, Ziyan Huang, Anlian Zhou, Yaming Jiang, Bangxing Zou, Binbin Liu, Cao Deng, Youhong Zhang.
      The silkworm (Bombyx mori) is not only an excellent model species, but also an important agricultural economic insect. Taking it as the research object, its advantages of low maintenance cost and no biohazard risks are considered. Small open reading frames (smORFs) are an important class of genomic elements that can produce bioactive peptides. However, the smORFs in silkworm had been poorly identified and studied. To further study the smORFs in silkworm, systematic genome-wide identification is essential. Here, we identified and analyzed smORFs in the silkworm using comprehensive methods. Our results showed that at least 738 highly reliable smORFs were found in B. mori and that 34,401 possible smORFs were partially supported. We also identified some differentially expressed and tissue-specific-expressed smORFs, which may be closely related to the characteristics and functions of the tissues. This article provides a basis for subsequent research on smORFs in silkworm, and also hopes to provide a reference point for future research methods for smORFs in other species.
    Keywords:  Bombyx mori; Peptides; Tissue-specific; smORFs
    DOI:  https://doi.org/10.7717/peerj.14682
  3. Nucleic Acids Res. 2023 Jan 18. pii: gkac1247. [Epub ahead of print]
    Annotation of uORFs in the OMIM genes allows to reveal pathogenic variants in 5'UTRs.
    Alexandra Filatova, Ivan Reveguk, Maria Piatkova, Daria Bessonova, Olga Kuziakova, Victoria Demakova, Alexander Romanishin, Veniamin Fishman, Yerzhan Imanmalik, Nikolay Chekanov, Rostislav Skitchenko, Yury Barbitoff, Olga Kardymon, Mikhail Skoblov.
      An increasing number of studies emphasize the role of non-coding variants in the development of hereditary diseases. However, the interpretation of such variants in clinical genetic testing still remains a critical challenge due to poor knowledge of their pathogenicity mechanisms. It was previously shown that variants in 5'-untranslated regions (5'UTRs) can lead to hereditary diseases due to disruption of upstream open reading frames (uORFs). Here, we performed a manual annotation of upstream translation initiation sites (TISs) in human disease-associated genes from the OMIM database and revealed ∼4.7 thousand of TISs related to uORFs. We compared our TISs with the previous studies and provided a list of 'high confidence' uORFs. Using a luciferase assay, we experimentally validated the translation of uORFs in the ETFDH, PAX9, MAST1, HTT, TTN,GLI2 and COL2A1 genes, as well as existence of N-terminal CDS extension in the ZIC2 gene. Besides, we created a tool to annotate the effects of genetic variants located in uORFs. We revealed the variants from the HGMD and ClinVar databases that disrupt uORFs and thereby could lead to Mendelian disorders. We also showed that the distribution of uORFs-affecting variants differs between pathogenic and population variants. Finally, drawing on manually curated data, we developed a machine-learning algorithm that allows us to predict the TISs in other human genes.
    DOI:  https://doi.org/10.1093/nar/gkac1247
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