bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2020‒10‒18
three papers selected by
Thomas Martinez
Salk Institute for Biological Studies

  1. Biochemistry. 2020 Oct 15.
      Proteogenomic identification of translated small open reading frames in humans has revealed thousands of microproteins, or polypeptides of fewer than 100 amino acids, that were previously invisible to geneticists. Hundreds of microproteins have been shown to be essential for cell growth and proliferation, and many regulate macromolecular complexes. One such regulatory microprotein is NBDY, a 68-amino acid component of the human cytoplasmic RNA decapping complex. Heterologously expressed NBDY was previously reported to regulate cytoplasmic ribonucleoprotein granules known as P-bodies and reporter gene stability, but the global effect of endogenous NBDY on the cellular transcriptome remained undefined. In this work, we demonstrate that endogenous NBDY directly interacts with the human RNA decapping complex through EDC4 and DCP1A and localizes to P-bodies. Global profiling of RNA stability changes in NBDY knockout (KO) cells reveals dysregulated stability of more than 1400 transcripts. DCP2 substrate transcript half-lives are both increased and decreased in NBDY KO cells, which correlates with 5' UTR length. NBDY deletion additionally alters the stability of non-DCP2 target transcripts, possibly as a result of downregulated expression of nonsense-mediated decay factors in NBDY KO cells. We present a comprehensive model of the regulation of RNA stability by NBDY.
  2. BMC Bioinformatics. 2020 Oct 14. 21(1): 455
      BACKGROUND: Small open reading frame (smORF) is open reading frame with a length of less than 100 codons. Microproteins, translated from smORFs, have been found to participate in a variety of biological processes such as muscle formation and contraction, cell proliferation, and immune activation. Although previous studies have collected and annotated a large abundance of smORFs, functions of the vast majority of smORFs are still unknown. It is thus increasingly important to develop computational methods to annotate the functions of these smORFs.RESULTS: In this study, we collected 617,462 unique smORFs from three studies. The expression of smORF RNAs was estimated by reannotated microarray probes. Using a speed-optimized correlation algorism, the functions of smORFs were predicted by their correlated genes with known functional annotations. After applying our method to 5 known microproteins from literatures, our method successfully predicted their functions. Further validation from the UniProt database showed that at least one function of 202 out of 270 microproteins was predicted.
    CONCLUSIONS: We developed a method, smORFunction, to provide function predictions of smORFs/microproteins in at most 265 models generated from 173 datasets, including 48 tissues/cells, 82 diseases (and normal). The tool can be available at .
    Keywords:  Function prediction; Gene expression; Microprotein; Small open reading frame
  3. Cancer Lett. 2020 Oct 07. pii: S0304-3835(20)30500-0. [Epub ahead of print]
      The human genome contains thousands of noncoding RNAs (ncRNAs), which are thought to lack open reading frames (ORFs) and cannot be translated. Some ncRNAs reportedly have important functions, including epigenetic regulation, chromatin remolding, protein modification, and RNA degradation, but the functions of most ncRNAs remain elusive. Through the application and development of ribosome profiling and sequencing technologies, an increasing number of studies have discovered the translation of ncRNAs. Although ncRNAs were initially defined as noncoding RNAs, a number of ncRNAs actually contain ORFs that are translated into peptides. Here, we summarize the available methods, tools, and databases for identifying and validating ncRNA-encoded peptides/proteins, and the recent findings regarding ncRNA-encoded small peptides/proteins in cancer are compiled and synthesized. Importantly, the role of ncRNA-encoding peptides/proteins has application prospects in cancer research, but some potential challenges remain unresolved. The aim of this review is to provide a theoretical basis that might promote the discovery of more peptides/proteins encoded by ncRNAs and aid the further development of novel diagnostic and prognostic cancer markers and therapeutic targets.
    Keywords:  Circular RNA; IRES; Long noncoding RNA; ORF; Ribosome sequencing; m6A