bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023‒07‒16
two papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. Int J Mol Sci. 2023 Jun 23. pii: 10562. [Epub ahead of print]24(13):
      Small open reading frames (sORFs) are often overlooked features in genomes. In the past, they were labeled as noncoding or "transcriptional noise". However, accumulating evidence from recent years suggests that sORFs may be transcribed and translated to produce sORF-encoded polypeptides (SEPs) with less than 100 amino acids. The vigorous development of computational algorithms, ribosome profiling, and peptidome has facilitated the prediction and identification of many new SEPs. These SEPs were revealed to be involved in a wide range of basic biological processes, such as gene expression regulation, embryonic development, cellular metabolism, inflammation, and even carcinogenesis. To effectively understand the potential biological functions of SEPs, we discuss the history and development of the newly emerging research on sORFs and SEPs. In particular, we review a range of recently discovered bioinformatics tools for identifying, predicting, and validating SEPs as well as a variety of biochemical experiments for characterizing SEP functions. Lastly, this review underlines the challenges and future directions in identifying and validating sORFs and their encoded micropeptides, providing a significant reference for upcoming research on sORF-encoded peptides.
    Keywords:  SEPs; coding potential prediction; micro-proteins; peptidome; sORF; sORF-encoded peptides; small (short) open reading frame
  2. Genes Dev. 2023 Jul 11.
      In addition to the main, protein-coding, open reading frame (mORF), many eukaryotic mRNAs contain upstream ORFs (uORFs) initiated at AUG or near-cognate codons residing 5' of the mORF start site. Whereas translation of uORFs generally represses translation of the mORFs, a subset of uORFs serves as a nexus for regulating translation of the mORF. In this review, we summarize the mechanisms by which uORFs can repress or stimulate mRNA translation, highlight uORF-mediated translational repression involving ribosome queuing, and critically evaluate recently described alternatives to the delayed reinitiation model for uORF-mediated regulation of the GCN4/ATF4 mRNAs.
    Keywords:  ATF4; GCN4; eIF2 phosphorylation; ribosome queuing; stringency; uORF