bims-micpro 2025-03-16 papers

RSC Chem Biol. 2025 Mar 06.

Identification of microproteins with transactivation activity by polyalanine motif selection.

Microproteins are an emerging class of proteins that are encoded by small open reading frames (smORFs) less than or equal to 100 amino acids. The functions of several microproteins have been illuminated through phenotypic screening or protein-protein interaction studies, but thousands of microproteins remain uncharacterized. The functional characterization of microproteins is challenging due to a lack of sequence homology. Here, we demonstrate a strategy to enrich microproteins that contain specific motifs as a means to more rapidly characterize microproteins. Specifically, we used the fact that polyalanine motifs are associated with nuclear proteins to select 58 candidate microproteins to screen for transactivation function. We identified three microproteins with transactivation activity when tested as GAL4-fusions in a cell-based luciferase assay. The results support the continued use of the motif selection strategy for the discovery of microprotein function.

DOI: https://doi.org/10.1039/d4cb00277f

Biochemistry (Mosc). 2025 Jan;90(1): 32-43

A Portrait of Three Mammalian Bicistronic mRNA Transcripts, Derived from the Genes ASNSD1, SLC35A4, and MIEF1.

Dmitry E Andreev, Ivan N Shatsky.

Recent advances in functional genomics have allowed identification of thousands of translated short open reading frames (sORFs) in the 5' leaders of mammalian mRNA transcripts. While most sORFs are unlikely to encode functional proteins, a small number have been shown to have evolved as protein-coding genes. As a result, dozens of these sORFs have already been annotated as protein-coding ORFs. mRNAs that contain both a protein-coding sORF and an annotated coding sequence (CDS) are referred to as bicistronic transcripts. In this study, we focus on three genes - ASNSD1, SLC35A4, and MIEF1 - which give rise to bicistronic mRNAs. We discuss recent findings regarding functional investigation of the corresponding polypeptide products, as well as how their translation is regulated, and how this unusual genetic arrangement may have evolved.

Keywords: bicistronic mRNA; dual coding; leaky scanning; reinitiation; translation initiation

DOI: https://doi.org/10.1134/S0006297924603630

Mol Med Rep. 2025 May;pii: 127. [Epub ahead of print]31(5):

Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review).

Yutong Ran, Zhiliang Guo, Lijuan Zhang, Hong Li, Xiaoyun Zhang, Xiumei Guan, Xiaodong Cui, Hao Chen, Min Cheng.

Mitochondria‑derived peptides (MDPs) are a unique class of peptides encoded by short open reading frames in mitochondrial DNA, including the mitochondrial open reading frame of the 12S ribosomal RNA type‑c (MOTS‑c). Recent studies suggest that MDPs offer therapeutic benefits in various diseases, including neurodegenerative disorders and types of cancer, due to their ability to increase cellular resilience. Mitochondrial dysfunction is a key factor in the onset and progression of cardiovascular diseases (CVDs), such as atherosclerosis and heart failure, as it disrupts energy metabolism, increases oxidative stress and promotes inflammation. MDPs such as humanin and MOTS‑c have emerged as important regulators of mitochondrial health, as they show protective effects against these processes. Recent studies have shown that MDPs can restore mitochondrial function, reduce oxidative damage and alleviate inflammation, thus counteracting the pathological mechanisms that drive CVDs. Therefore, MDPs hold promise as therapeutic agents that are capable of slowing, stopping, or even reversing CVD progression and their use presents a promising strategy for future treatments. However, the clinical application of MDPs remains challenging due to their low bioavailability, poor stability and high synthesis costs. Thus, it is necessary to improve drug delivery systems to enhance the bioavailability of MDPs. Moreover, integrating basic research with clinical trials is essential to bridge the gap between experimental findings and clinical applications.

Keywords: cardiovascular diseases; inflammation; mechanism; mitochondria; mitochondria‑derived peptides

DOI: https://doi.org/10.3892/mmr.2025.13492

Trends Microbiol. 2025 Mar 06. pii: S0966-842X(25)00011-3. [Epub ahead of print]

Small proteins and peptides conferring protection against antimicrobial compounds.

Rianne C Prins, Sonja Billerbeck.

The secretion of antimicrobials is widespread among microorganisms, many of which have developed protection mechanisms. While well-characterized protection mechanisms involve relatively large proteins - such as exporters or compound- or target-modifying enzymes - we discuss how small proteins and peptides can also confer protection. Recent technological advances have revealed the functional capacity and importance of the small proteome, as well as its potential for de novo evolution. We consolidate examples of diverse small proteins that play a protective role against antimicrobial agents, highlighting characteristics and exploring their mechanisms of protection where data are available. We advocate for further examination of their mechanisms of protection as they may constitute an intriguing, mechanistically, and evolutionary distinct part of the antimicrobial resistome.

Keywords: antimicrobial resistance; antitoxin; immunity protein; sORF; self-protection; small protein

DOI: https://doi.org/10.1016/j.tim.2025.01.011

J Integr Plant Biol. 2025 Mar 10.

Decoding small peptides: Regulators of plant growth and stress resilience.

Fei Xiao, Huapeng Zhou, Honghui Lin.

Small peptides (SPs) are pivotal signaling molecules that play essential roles in the precise regulation of plant growth, development, and stress responses. Recent advancements in sequencing technologies, bioinformatics approaches, and biochemical and molecular techniques have significantly enhanced the accuracy of SP identification, unveiling their diverse biological functions in plants. This review provides a comprehensive overview of the characteristics and methodologies for identifying SPs in plants. It highlights recent discoveries regarding the biological roles and signaling pathways of SPs in regulating plant growth, development, and plant-microbial interactions, as well as their contributions to plant resilience under various environmental stresses, including abiotic stress, nutrient deficiencies, and biotic challenges. Additionally, we discuss current insights into the potential applications of SPs and outline future research directions aimed at leveraging these molecules to enhance plant adaptation to environmental challenges. By integrating recent findings, this review lays a foundation for advancing the understanding and utilization of SPs to improve plant resilience and productivity.

Keywords: abiotic and biotic stress responses; crop improvement; plant developmental regulation; plant–microbe interactions; small peptide signaling

DOI: https://doi.org/10.1111/jipb.13873

Am J Respir Cell Mol Biol. 2025 Mar 12.

A Mighty Mitochondrial Microprotein: The Protective Role of MOTS-C in Acute Lung Injury.

Corrine Kliment.

Keywords: Acute lung injury; Ferroptosis; Glycolysis; MOTS-C

DOI: https://doi.org/10.1165/rcmb.2025-0062ED

Front Plant Sci. 2025 ;16 1506617

Peptides in plant reproduction-small yet powerful.

Chun-Lin Yan, Kai-Xun Guan, Hong Lin, Ting Feng, Jiang-Guo Meng.

Peptides, currently being considered as a novel class of plant hormones, play diverse roles in plant growth and development. Peptides trigger signaling by binding to receptors and co-receptors, thus activating cellular signaling pathways. Recently, peptides have been extensively investigated in plant reproduction-related processes, ranging from gametes development to gametes fusion. In this review, we summarize recent advancements related to the role of peptides in plant reproduction and discuss challenges that need to be addressed urgently.

Keywords: fertilization; peptide; plant reproduction; pollen tube; receptor

DOI: https://doi.org/10.3389/fpls.2025.1506617