bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2022–12–04
two papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Ribo-uORF: a comprehensive data resource of upstream open reading frames (uORFs) based on ribosome profiling.
  2. Casting CRISPR-Cas13d to fish for microprotein functions in animal development.
  1. Nucleic Acids Res. 2022 Nov 28. pii: gkac1094. [Epub ahead of print]
    Ribo-uORF: a comprehensive data resource of upstream open reading frames (uORFs) based on ribosome profiling.
    Qi Liu, Xin Peng, Mengyuan Shen, Qian Qian, Junlian Xing, Chen Li, Richard I Gregory.
      Upstream open reading frames (uORFs) are typically defined as translation sites located within the 5' untranslated region upstream of the main protein coding sequence (CDS) of messenger RNAs (mRNAs). Although uORFs are prevalent in eukaryotic mRNAs and modulate the translation of downstream CDSs, a comprehensive resource for uORFs is currently lacking. We developed Ribo-uORF (http://rnainformatics.org.cn/RiboUORF) to serve as a comprehensive functional resource for uORF analysis based on ribosome profiling (Ribo-seq) data. Ribo-uORF currently supports six species: human, mouse, rat, zebrafish, fruit fly, and worm. Ribo-uORF includes 501 554 actively translated uORFs and 107 914 upstream translation initiation sites (uTIS), which were identified from 1495 Ribo-seq and 77 quantitative translation initiation sequencing (QTI-seq) datasets, respectively. We also developed mRNAbrowse to visualize items such as uORFs, cis-regulatory elements, genetic variations, eQTLs, GWAS-based associations, RNA modifications, and RNA editing. Ribo-uORF provides a very intuitive web interface for conveniently browsing, searching, and visualizing uORF data. Finally, uORFscan and UTR5var were developed in Ribo-uORF to precisely identify uORFs and analyze the influence of genetic mutations on uORFs using user-uploaded datasets. Ribo-uORF should greatly facilitate studies of uORFs and their roles in mRNA translation and posttranscriptional control of gene expression.
    DOI:  https://doi.org/10.1093/nar/gkac1094
  2. iScience. 2022 Dec 22. 25(12): 105547
    Casting CRISPR-Cas13d to fish for microprotein functions in animal development.
    Anthony James Treichel, Ariel Alejandro Bazzini.
      Protein coding genes were originally identified with sequence-based definitions that included a 100-codon cutoff to avoid annotating irrelevant open reading frames. However, many active proteins contain less than 100 amino acids. Indeed, functional genetics, ribosome profiling, and proteomic profiling have identified many short, translated open reading frames, including those with biologically active peptide products (microproteins). Yet, functions for most of these peptide products remain unknown. Because microproteins often act as key signals or fine-tune processes, animal development has already revealed functions for a handful of microproteins and provides an ideal context to uncover additional microprotein functions. However, many mRNAs during early development are maternally provided and hinder targeted mutagenesis approaches to characterize developmental microprotein functions. The recently established, RNA-targeting CRISPR-Cas13d system in zebrafish overcomes this barrier and produces potent knockdown of targeted mRNA, including maternally provided mRNA, and enables flexible, efficient interrogation of microprotein functions in animal development.
    Keywords:  Complex system biology; Developmental biology; Genetics
    DOI:  https://doi.org/10.1016/j.isci.2022.105547
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