bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2022‒07‒03
four papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. PLoS One. 2022 ;17(6): e0269404
      Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity-Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Further, we find that Pants is secreted from neurons, where it associates with synapses but is rapidly degraded with stimulation. Pants dynamically interacts with Rtn4/Nogo-A, a well-studied regulator of adult plasticity. Pants interaction with Nogo-A augments its influence over postsynaptic AMPA receptor clustering, thus gating plasticity at adult synapses. This work shows that neural micropeptides can act as architectural modules that increase the functional diversity of the known proteome.
  2. Front Mol Biosci. 2022 ;9 817517
      Long non-coding RNAs (lncRNAs) were originally defined as non-coding RNAs (ncRNAs) which lack protein-coding ability. However, with the emergence of technologies such as ribosome profiling sequencing and ribosome-nascent chain complex sequencing, it has been demonstrated that most lncRNAs have short open reading frames hence the potential to encode functional micropeptides. Such micropeptides have been described to be widely involved in life-sustaining activities in several organisms, such as homeostasis regulation, disease, and tumor occurrence, and development, and morphological development of animals, and plants. In this review, we focus on the latest developments in the field of lncRNA-encoded micropeptides, and describe the relevant computational tools and techniques for micropeptide prediction and identification. This review aims to serve as a reference for future research studies on lncRNA-encoded micropeptides.
    Keywords:  Ribo-seq; coding potential prediction; lncRNA; micropeptide; sORF
  3. Nat Commun. 2022 Jun 29. 13(1): 3751
      Some circular RNAs (circRNAs) were found to be translated through IRES-driven mechanism, however the scope and functions of circRNA translation are unclear because endogenous IRESs are rare. To determine the prevalence and mechanism of circRNA translation, we develop a cell-based system to screen random sequences and identify 97 overrepresented hexamers that drive cap-independent circRNA translation. These IRES-like short elements are significantly enriched in endogenous circRNAs and sufficient to drive circRNA translation. We further identify multiple trans-acting factors that bind these IRES-like elements to initiate translation. Using mass-spectrometry data, hundreds of circRNA-coded peptides are identified, most of which have low abundance due to rapid degradation. As judged by mass-spectrometry, 50% of translatable endogenous circRNAs undergo rolling circle translation, several of which are experimentally validated. Consistently, mutations of the IRES-like element in one circRNA reduce its translation. Collectively, our findings suggest a pervasive translation of circRNAs, providing profound implications in translation control.
  4. Biochim Biophys Acta Rev Cancer. 2022 Jun 28. pii: S0304-419X(22)00080-4. [Epub ahead of print] 188755
      With technological advances, previously neglected noncanonical open reading frames (nORFs) are drawing ever-increasing attention. However, the translation potential of numerous putative nORFs remains elusive, and the functions of noncanonical peptides have not been systemically summarized. Moreover, the relationship between noncanonical peptides and their counterpart protein or RNA products remains elusive and the clinical implementation of noncanonical peptides has not been explored. In this review, we highlight how recent technological advances such as ribosome profiling, bioinformatics approaches and CRISPR/Cas9 facilitate the research of noncanonical peptides. We delineate the features of each nORF category and the evolutionary process underneath the nORFs. Most importantly, we summarize the diversified functions of noncanonical peptides in cancer based on their subcellular location, which reflect their extensive participation in key pathways and essential cellular activities in cancer cells. Meanwhile, the equilibrium between noncanonical peptides and their corresponding transcripts or counterpart products may be dysregulated under pathological states, which is essential for their roles in cancer. Lastly, we explore their underestimated potential in clinical application as diagnostic biomarkers and treatment targets against cancer.
    Keywords:  Cancer; Micropeptide; Noncanonical open reading frame; Noncanonical peptide; circRNA