bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023–12–17
three papers selected by
Thomas Farid Martínez, University of California, Irvine



  1. BMC Bioinformatics. 2023 Dec 13. 24(1): 471
       BACKGROUND: In canonical protein translation, ribosomes initiate translation at a specific start codon, maintain a single reading frame throughout elongation, and terminate at the first in-frame stop codon. However, ribosomal behavior can deviate at each of these steps, sometimes in a programmed manner. Certain mRNAs contain sequence and structural elements that cause ribosomes to begin translation at alternative start codons, shift reading frame, read through stop codons, or reinitiate on the same mRNA. These processes represent important translational control mechanisms that can allow an mRNA to encode multiple functional protein products or regulate protein expression. The prevalence of these events remains uncertain, due to the difficulty of systematic detection.
    RESULTS: We have developed a computational model to infer non-canonical translation events from ribosome profiling data.
    CONCLUSION: ORFeus identifies known examples of alternative open reading frames and recoding events across different organisms and enables transcriptome-wide searches for novel events.
    Keywords:  Alternative ORF; HMM; Non-canonical ORF; Ribosome profiling
    DOI:  https://doi.org/10.1186/s12859-023-05602-8
  2. Cancers (Basel). 2023 Dec 01. pii: 5689. [Epub ahead of print]15(23):
      Alternative splicing can produce transcripts that affect cancer development and thus shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been studied less in cancer biology research. Here, we generated a pan-cancer IR landscape for more than 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). We characterized differentially retained introns between tumor and normal samples and identified retained introns associated with survival. We discovered 988 differentially retained introns in 14 cancers, some of which demonstrated diagnostic potential in multiple cancer types. We also inferred a large number of prognosis-related introns in 33 cancer types, and the associated genes included well-known cancer hallmarks such as angiogenesis, metastasis, and DNA mutations. Notably, we discovered a novel intron retention inside the 5'UTR of STN1 that is associated with the survival of lung cancer patients. The retained intron reduces translation efficiency by producing upstream open reading frames (uORFs) and thereby inhibits colony formation and cell migration of lung cancer cells. Besides, the IR-based prognostic model achieved good stratification in certain cancers, as illustrated in acute myeloid leukemia. Taken together, we performed a comprehensive IR survey at a pan-cancer level, and the results implied that IR has the potential to be diagnostic and prognostic cancer biomarkers, as well as new drug targets.
    Keywords:  RNA-seq; cancer; diagnosis; intron retention; prognosis
    DOI:  https://doi.org/10.3390/cancers15235689
  3. Plants (Basel). 2023 Nov 23. pii: 3951. [Epub ahead of print]12(23):
      Biotic stress tolerance in plants is complex as it relies solely on specific innate immune responses from different plant species combating diverse pathogens. Each component of the plant immune system is crucial to comprehend the molecular basis underlying sustainable resistance response. Among many other regulatory components, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have recently emerged as novel regulatory control switches in plant development and stress biology. Besides, miPs, the small peptides (100-150 amino acids long) encoded by some of the non-coding portions of the genome also turned out to be paramount regulators of plant stress. Although some studies have been performed in deciphering the role of miPs in abiotic stress tolerance, their function in regulating biotic stress tolerance is still largely elusive. Hence, the present review focuses on the roles of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in combating biotic stress in plants. The probable role of miPs in plant-microbe interaction is also comprehensively highlighted. This review enhances our current understanding of plant lncRNAs, circRNAs, and miPs in biotic stress tolerance and raises intriguing questions worth following up.
    Keywords:  biotic stress; miPEPs; miRNA; micropeptides; plant–microbe interaction
    DOI:  https://doi.org/10.3390/plants12233951