bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2024–12–22
four papers selected by
Thomas Farid Martínez, University of California, Irvine



  1. Database (Oxford). 2024 Dec 17. pii: baae123. [Epub ahead of print]2024
      Non-coding RNAs (ncRNAs) are traditionally considered incapable of encoding proteins, but new evidence suggests that small open reading frames (sORFs) within ncRNAs can actually encode biologically functional small peptides. Despite growing recognition of their importance, a systematic exploration of plant ncRNAs with coding potential has remained largely uncharted territory, especially in the context of their translational activities. By collecting and analyzing Ribo-Seq data from 226 Arabidopsis thaliana samples, we have integrated extensive information on Arabidopsis ncRNAs with coding potential and developed the AthRiboNC database, a novel and dedicated database that consolidates extensive information on ncRNAs with coding potential in Arabidopsis. AthRiboNC covers detailed information on 2743 long non-coding RNAs, 255 microRNAs, and 1871 circular RNA in Arabidopsis, along with 40 162 ORFs identified from these ncRNAs. The database also constructs co-expression networks for ncRNAs with coding potential, revealing correlations and potential biological function interpretations. With a commitment to accessibility and ease-of-use, AthRiboNC features a clear and intuitive interface. We hope that AthRiboNC will serve as a valuable resource for exploring the coding potential of plant ncRNAs. Database URL: https://bis.zju.edu.cn/athribonc.
    DOI:  https://doi.org/10.1093/database/baae123
  2. Cells. 2024 Nov 28. pii: 1966. [Epub ahead of print]13(23):
      The identification of small proteins and proteins produced from unannotated open reading frames (called alternative proteins or AltProts) has changed our vision of the proteome and has attracted more and more attention from the scientific community. Despite several studies investigating particular AltProts in diseases and demonstrating their importance in such context, we are still missing data on their expression and functions in many pathologies. Among these, pancreatic ductal adenocarcinoma (PDAC) is a particularly relevant case to study alternative proteins. Indeed, late detection of this disease, notably due to the lack of reliable biomarkers of early-stage PDAC, and the fact that tumors rapidly develop resistance to most of the treatments used in the clinics warrant the exploration of new repertoires of molecules. In the present article, we aim to investigate the alternative proteome of pancreatic cancer cell lines as a first attempt to decipher the expression of AltProts in PDAC. Thanks to a combined data-dependent and data-independent acquisition mass spectrometry workflow, we were able to identify tryptic peptides matching 113 AltProts in a panel of 6 cell lines. In addition, we identified AltProts differentially expressed between pancreatic cancer cell lines and other cells (HeLa and HEK293T). Finally, mining the TCGA and Gtex databases showed that the corresponding transcripts encoding several AltProts we identified are differentially expressed between PDAC tumors and normal tissues and are correlated with the patient's survival.
    Keywords:  alternative proteins; data independent acquisition; microproteins; pancreatic ductal adenocarcinoma; proteomics; short open reading frame-encoded peptides
    DOI:  https://doi.org/10.3390/cells13231966
  3. Trends Genet. 2024 Dec 16. pii: S0168-9525(24)00292-0. [Epub ahead of print]
      Given the uniqueness of the mitochondria, and the fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery of an increasing number of microproteins from this organelle and the importance of mitochondria to cellular and organismal health make it a priority to study this novel class of proteins in search of possible therapeutic targets and cures. In this review, we discuss the history of MDP discovery, describe the function of each MDP, and conclude with future goals and techniques to help discover more MDPs.
    Keywords:  aging; microprotein; mitochondria
    DOI:  https://doi.org/10.1016/j.tig.2024.11.010
  4. J Exp Bot. 2024 Dec 17. pii: erae501. [Epub ahead of print]
      In order to develop a sustainable agriculture respecting the environment and to reduce chemical inputs, a new strategy has emerged in recent years, based on the use of products targeting plants' natural defense and growth mechanisms. In this context, a few years ago we demonstrated the existence in plants of regulatory peptides called miPEPs for "microRNA-encoded peptides". MicroRNAs (miRNAs) are small RNAs that down-regulate the expression of numerous genes in eukaryotes. MiPEPs increase the amount of their cognate miRNA, resulting in an even greater decrease in the expression of genes targeted by these miRNAs. Thus, the application of an artificial miPEP to a plant causes a phenotype associated with a change in the genes targeted by the corresponding miRNA. More recently we also identified new regulatory peptides, namely cPEPs for "complementary peptides", capable of enhancing the activity of a given protein, independently of any increase in transcriptional activity. Moreover, as for the miPEPs, the external application of these new peptides makes it possible to regulate the phenotypes associated with the targeted proteins. This review highlights the most recent advances in the potential use of miPEPs and cPEPs in agronomy to improve plant development and stress tolerance.
    Keywords:  bio-stimulant; biotechnology; cPEP; complementary peptide; gene regulation; miPEP; miRNA; microRNA-encoded peptide; peptide; plant
    DOI:  https://doi.org/10.1093/jxb/erae501