bims-micpro 2026-06-21 papers

EMBO J. 2026 Jun 19.

The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.

Leoš Shivaya Valášek, Filip Brázdovič, Filip Trčka, Mahabub Pasha Mohammad, Adriana Roithová.

From a historical perspective, long non-coding RNAs (lncRNAs) represent a relatively short story. However, this story has many plot lines, thrills, twists, and turns that altogether form quite a long saga of its own. lncRNAs stay at the forefront of a recent paradigm shift from a protein-only world to the mysterious RNA world, the enormous complexity of which we are only beginning to appreciate. Here, we review the most enigmatic aspect of lncRNAs, their coding ability in the context of whole-cell regulation. What peptides do lncRNAs encode as true translons? What is the mechanism of their translation? What roles do these ncRNA-encoded peptides (ncPEPs) play during differentiation and development and in distinct pathologies? Do these ncPEPs contribute to the already known regulatory roles of lncRNAs? Shouldn't we coin the coding subset of lncRNAs its apt name: cryptic long non-coding RNAs (crpt-lncRNAs) for their cryptic coding capacity? These and other questions concerning these current winners of the spotlight in molecular biology, which await resolution, are discussed so that molecular history can be rewritten once again.

DOI: https://doi.org/10.1038/s44318-026-00826-9

Transl Cancer Res. 2026 May 30. 15(5): 394

Micropeptide colorectal neoplasia differentially expressed (CRNDE) 84aa encoded by CRNDE elicits a T-cell immune response to breast cancer.

Lili Zeng, Peng Hu, Changsong Bai, Yujia Luo, Xinyu Fang, Xinyu Liu, Qingyi Yuan, Xiaofeng Zhu.

Background: The activation of anti-tumor immunity by tumor antigens is central to cancer immunotherapy. Cryptic peptides from non-coding regions represent potential antigens, with long non-coding RNAs (lncRNAs) emerging as a novel source of such peptides. This study aims to demonstrate that specific lncRNAs overexpressed in immunologically "cold" tumors-breast cancer, encode immunogenic peptides capable of activating anti-tumor immune responses.
Methods: We identified elevated colorectal neoplasia differentially expressed (CRNDE) expression in breast cancer via database mining and polymerase chain reaction (PCR). Plasmid transfection and Western blot confirmed CRNDE peptide production. The immunogenicity of the peptide was assessed by enzyme-linked immunospot (ELISpot) and flow cytometry, while its ability to activate cytotoxic T lymphocytes (CTLs) was evaluated through flow cytometry and lactate dehydrogenase (LDH) release assays. Immunohistochemistry (IHC) and Western blot verified high expression of the CRNDE encodes an 84-amino acid peptide (CRNDE 84aa) peptide in breast cancer. Finally, patient-derived xenograft (PDX) models were used to validate in vivo tumor suppression mediated by CRNDE 84aa-activated CTLs.
Results: We demonstrated that lncRNA CRNDE 84aa. A predicted HLA-A*02:01-restricted epitope of CRNDE 84aa induced a specific human T-cell response. CTLs from a breast cancer patient recognized the CRNDE 84aa epitope (FIMELLYWL) and lysed HLA-A2-positive breast cancer cells expressing CRNDE 84aa. Furthermore, human CD8+ T cells enriched with prioritized cryptic breast cancer antigens protected mice from tumor challenge in autologous PDX models.
Conclusions: CRNDE 84aa is highly expressed in breast cancer and functions as a tumor antigen that activates anti-tumor immunity. This study suggests that lncRNA-encoded peptides represent a viable source of tumor antigens for immunologically "cold" tumors such as breast cancer, highlighting their potential as novel targets for immunotherapy.

Keywords: Tumor antigen; breast cancer; cryptic peptide; immunotherapy; long non-coding RNA (lncRNA)

DOI: https://doi.org/10.21037/tcr-2025-1-2809

Exp Physiol. 2026 Jun 19.

Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model.

Aimee R Mills, Antonio de Souza, Toan Pham, Odunayo O Mugisho.

Type 2 diabetes mellitus (T2DM) is associated with chronic systemic and cardiac inflammation, contributing to the development of diabetic cardiomyopathy. The mitochondrial-derived peptide mitochondrial open reading frame of the 12S rRNA type-C (MOTS-c) has emerged as a promising regulator of metabolic and inflammatory pathways. In this study, we investigated the effects of MOTS-c treatment on leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome activity in a high-fat diet and streptozotocin-induced T2DM rat model. MOTS-c treatment significantly reduced fasting blood glucose and circulating C-reactive protein levels, while selectively modulating plasma inflammatory cytokines, including interleukin (IL)-10 and IL-1β. Immunohistochemical analysis revealed reduced levels of NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and cleaved caspase-1 in left ventricular tissue following MOTS-c administration. Correlation analyses linked IL-18 and IL-1β with elevated markers, including low-density lipoprotein and uric acid, suggesting interplay between overall health and inflammasome activity. These results indicate that MOTS-c modulates both systemic and cardiac inflammation in T2DM, providing a novel therapeutic approach for reducing cardiovascular risk in diabetic patients.

Keywords: MOTS‐c; diabetic heart; inflammasome; inflammation

DOI: https://doi.org/10.1113/EP093714

Plant Commun. 2026 Jun 15. pii: S2590-3462(26)00277-4. [Epub ahead of print] 101969

A wheat lncRNA-encoded peptide promotes autophagy and targets viral NIb for degradation to confer antiviral resistance.

Juan Zhang, Peng Liu, Bin Yong, Yaoyao Li, Chunyan Qi, Zechi Wu, Zengxu Wu, Tianye Zhang, Lixiao Feng, Lidan Guo, Fangfang Li, Chuanxi Zhang, Tianbo Liu, Jianping Chen, Jian Yang.

Long noncoding RNAs (lncRNAs) are increasingly recognized as a source of functional peptides involved in plant development and immunity, yet little is known about whether lncRNA-encoded peptides participate in antiviral defence. By transcriptome analysis with peptide-coding potential prediction, we identify lncRNA19864, which is highly expressed in wheat yellow mosaic virus (WYMV)-resistant cultivars and encodes a 39-amino-acid peptide, TaLEP1. Genetic manipulation of TaLEP1 expression showed that TaLEP1 as a positive regulator of wheat resistance to WYMV. Mechanistically, TaLEP1 forms oligomers and interacts with both the host autophagy factor TaATG18a and the viral replicase NIb, thereby facilitating NIb recruitment to autophagosomes for degradation. Disruption of TaLEP1 oligomerization or TaATG18a function impaired NIb degradation and compromised TaLEP1-mediated antiviral resistance. Notably, TaLEP1 also confers resistance to other Potyviridae members, including Turnip mosaic virus (TuMV) and Soybean mosaic virus (SMV), by similarly targeting their NIb proteins for degradation. Accordingly, lncRNA-encoded peptide is involved in plant antiviral immunity. Our results offer a potential strategy for engineering broad-spectrum virus resistance in crops.

Keywords: NIb; TaLEP1; antiviral immunity; autophagy; peptides

DOI: https://doi.org/10.1016/j.xplc.2026.101969

Gen Comp Endocrinol. 2026 Jun 13. pii: S0016-6480(26)00089-4. [Epub ahead of print] 114962

Roles of the FAM237-derived small proteins in energy homeostasis: a comparative perspective of neurosecretory protein GL and GM across vertebrates.

Yuki Narimatsu, Eiko Iwakoshi-Ukena, Kazuyoshi Ukena.

Hypothalamic neuropeptides and neural circuits integrate peripheral signals, nutrient demand, and environmental cues to orchestrate energy homeostasis in vertebrates. Neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are hypothalamic small secretory proteins encoded by paralogous genes of the FAM237 family. These genes were initially identified in birds, but database search showed evolutionary conservation across vertebrates, suggesting conserved physiological roles for NPGL and NPGM. Previous studies on NPGL have demonstrated that NPGL stimulates overeating and fat accumulation in a diet- and strain-dependent manner in both mammals and birds. Accumulating evidence suggests that NPGM may also be involved in hyperphagia and adiposity. Notably, recent progress in transcriptomics and histological analyses has revealed expression of Npgl and Npgm in specific hypothalamic neuronal subpopulations involved in energy homeostasis. Here, we summarize recent progress in understanding the metabolic actions of NPGL and NPGM. We then focus on the cellular identity of Npgl- and Npgm-expressing neurons. Finally, we discuss future directions and potential molecular mechanisms of metabolic regulation by NPGL and NPGM. Investigating the NPGL/NPGM system, which regulates energy metabolism, will contribute to understanding both conserved and species-specific mechanisms of energy homeostasis across vertebrates.

Keywords: FAM237 family; Fat accumulation; Feeding behavior; Hypothalamus; Neuropeptide; Neurosecretory protein GL; Neurosecretory protein GM

DOI: https://doi.org/10.1016/j.ygcen.2026.114962

Nat Rev Nephrol. 2026 Jun 18.

The versatile roles of long non-coding RNAs in kidney disease.

Wai Han Yiu, Sydney C W Tang.

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of kidney homeostasis, and their dysregulation has been implicated in a wide range of kidney diseases including acute kidney injury, chronic kidney disease and renal cell carcinoma, as well as in age-related kidney dysfunction. Increasing evidence indicates that lncRNAs have roles in key cellular processes including inflammation, autophagy, cell proliferation, senescence, apoptosis, mitochondrial dysfunction, angiogenesis, epithelial-mesenchymal transition and interstitial fibrosis. LncRNAs interact with RNA, DNA and protein to regulate gene expression via multiple mechanisms, including RNA modifications, scaffold assembly, chromatin remodelling, transcription and post-transcriptional control. Beyond their non-coding functions, some lncRNAs can be translated into bioactive micropeptides that further modulate cellular activity. Given their tissue-specific expression and high stability in body fluids, lncRNAs hold promise as biomarkers for early detection and monitoring of kidney diseases. Furthermore, lncRNA-based therapies offer novel opportunities to halt disease progression in chronic kidney disease and overcome drug resistance in renal cell carcinoma. Improved understanding of lncRNA-mediated disease mechanisms could therefore lead to improvements in the diagnosis and treatment of kidney pathologies.

DOI: https://doi.org/10.1038/s41581-026-01094-w