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Cells
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Microproteins: From Identification to the Discovery of Their Functions
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Microproteins: From Identification to the Discovery of Their Functions

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (25 February 2025) | Viewed by 4722

Special Issue Editor

Dr. Bertrand Fabre

E-Mail Website
Guest Editor
Laboratoire de Recherche en Sciences Végétales (LRSV), CNRS/UT3/INPT, 31320 Auzeville-Tolosane, France
Interests: microproteins; alternative proteins; mass spectrometry; protein complexes

Special Issue Information

Dear Colleagues,

Over the past few years, the landscape of the proteome (ensemble of proteins) has undergone a transformative shift with the revelation of the pervasive expression of microproteins in many species. These small proteins appear to be important players in key cellular processes. Hidden for a long time due to technological limitations, these small yet potent entities have emerged as pivotal regulators, captivating the scientific community's interest and inspiring a new wave of research.

Microproteins (also known as alternative proteins or short open reading frame-encoded peptides (SEPs)), typically defined as yet non-annotated proteins with fewer than 100 amino acids, have challenged traditional views on protein expression and the functional significance of small peptides. Technological advancements in ribosome profiling, mass spectrometry, transcriptomics, and functional genomics have redefined our ability to identify and characterize microproteins. This Special Issue aims to showcase the latest breakthroughs in the field, providing a platform for researchers to share insights into the identification, characterization, and functional elucidation of microproteins.

The scope of this Special Issue encompasses a diverse array of topics within the realm of microproteins, including, but not limited to, the following:

  1. Identification techniques: Cutting-edge methodologies for the accurate identification and quantification of microproteins;
  2. Functional characterization: Investigations into the diverse roles and molecular mechanisms through which microproteins exert their influence on cellular processes;
  3. Evolutionary conservation: Explorations of the evolutionary conservation and divergence of microproteins across species;
  4. Technological innovations: Discussions of novel technologies and tools driving advancements in microprotein research;
  5. Emerging trends: Highlighting emerging trends and future directions in the study of microproteins.

We invite researchers, academicians, and practitioners to contribute original research articles, reviews, and communications that advance our understanding of microproteins and their roles in cellular function. 

Dr. Bertrand Fabre
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microproteins
  • short open reading frame-encoded peptides (SEPs)
  • alternative proteins
  • functional characterization
  • mass spectrometry
  • transcriptomics
  • ribosome profiling
  • functional genomics
  • molecular mechanisms
  • cellular processes
  • signaling pathways
  • cellular homeostasis
  • protein–protein interactions

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Published Papers (3 papers)

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Research

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23 pages, 6130 KiB  
Article
Pervasiveness of Microprotein Function Amongst Drosophila Small Open Reading Frames (SMORFS)
by Ana Isabel Platero, Jose Ignacio Pueyo, Sarah Anne Bishop, Emile Gerard Magny and Juan Pablo Couso
Cells 2024, 13(24), 2090; https://doi.org/10.3390/cells13242090 - 18 Dec 2024
Viewed by 964
Abstract
Small Open Reading Frames (smORFs) of less than 100 codons remain mostly uncharacterised. About a thousand smORFs per genome encode peptides and microproteins about 70–80 aa long, often containing recognisable protein structures and markers of translation, and these are referred to as short [...] Read more.
Small Open Reading Frames (smORFs) of less than 100 codons remain mostly uncharacterised. About a thousand smORFs per genome encode peptides and microproteins about 70–80 aa long, often containing recognisable protein structures and markers of translation, and these are referred to as short Coding Sequences (sCDSs). The characterisation of individual sCDSs has provided examples of smORFs’ function and conservation, but we cannot infer the functionality of all other metazoan smORFs from these. sCDS function has been characterised at a genome-wide scale in yeast and bacteria, showing that hundreds can produce a phenotype, but attempts in metazoans have been less successful. Either most sCDSs are not functional, or classic experimental techniques do not work with smORFs due to their shortness. Here, we combine extensive proteomics with bioinformatics and genetics in order to detect and corroborate sCDS function in Drosophila. Our studies nearly double the number of sCDSs with detected peptides and microproteins and an experimentally corroborated function. Finally, we observe a correlation between proven sCDS protein function and bioinformatic markers such as conservation and GC content. Our results support that sCDSs peptides and microproteins act as membrane-related regulators of canonical proteins, regulators whose functions are best understood at the cellular level, and whose mutants produce little, if any, overt morphological phenotypes. Full article
(This article belongs to the Special Issue Microproteins: From Identification to the Discovery of Their Functions)
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14 pages, 3249 KiB  
Article
Mass Spectrometry-Based Workflow for the Identification and Quantification of Alternative and Canonical Proteins in Pancreatic Cancer Cells
by Clémence Guillon, Carole Pichereaux, Ikrame Lazar, Karima Chaoui, Emmanuelle Mouton-Barbosa, Mehdi Liauzun, Edith Gourbeyre, Pinar Altiner, David Bouyssié, Alexandre Stella, Odile Burlet-Schiltz, Serge Plaza, Yvan Martineau and Bertrand Fabre
Cells 2024, 13(23), 1966; https://doi.org/10.3390/cells13231966 - 28 Nov 2024
Viewed by 1314
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Microproteins: From Identification to the Discovery of Their Functions)
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Review

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16 pages, 1986 KiB  
Review
Small ORFs, Big Insights: Drosophila as a Model to Unraveling Microprotein Functions
by Hélène Chanut-Delalande and Jennifer Zanet
Cells 2024, 13(19), 1645; https://doi.org/10.3390/cells13191645 - 2 Oct 2024
Cited by 1 | Viewed by 1558
Abstract
Recently developed experimental and computational approaches to identify putative coding small ORFs (smORFs) in genomes have revealed thousands of smORFs localized within coding and non-coding RNAs. They can be translated into smORF peptides or microproteins, which are defined as less than 100 amino [...] Read more.
Recently developed experimental and computational approaches to identify putative coding small ORFs (smORFs) in genomes have revealed thousands of smORFs localized within coding and non-coding RNAs. They can be translated into smORF peptides or microproteins, which are defined as less than 100 amino acids in length. The identification of such a large number of potential biological regulators represents a major challenge, notably for elucidating the in vivo functions of these microproteins. Since the emergence of this field, Drosophila has proved to be a valuable model for studying the biological functions of microproteins in vivo. In this review, we outline how the smORF field emerged and the nomenclature used in this domain. We summarize the technical challenges associated with identifying putative coding smORFs in the genome and the relevant translated microproteins. Finally, recent findings on one of the best studied smORF peptides, Pri, and other microproteins studied so far in Drosophila are described. These studies highlight the diverse roles that microproteins can fulfil in the regulation of various molecular targets involved in distinct cellular processes during animal development and physiology. Given the recent emergence of the microprotein field and the associated discoveries, the microproteome represents an exquisite source of potentially bioactive molecules, whose in vivo biological functions can be explored in the Drosophila model. Full article
(This article belongs to the Special Issue Microproteins: From Identification to the Discovery of Their Functions)
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