bims-musmir 2025-09-28 papers

bims-musmir

Biomed News

on microRNAs in muscle

Issue of 2025–09–28
eleven papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway

Fiber-type vulnerability and proteostasis reprogramming in skeletal muscle during pancreatic cancer cachexia.
The multimodal transcriptional response of denervated skeletal muscle involves regulation of Gramd1 genes impacting muscle size.
Hepatic ketogenic insufficiency blunts exercise-induced energy expenditure and alters mitochondrial proteins in skeletal muscle.
Isolation of functional lysosomes from skeletal muscle.
Semaglutide impacts skeletal muscle to a similar extent as caloric restriction in mice with diet-induced obesity.
Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism.
Vascular adhesion molecule 1+ fibro-adipogenic progenitors mark fatty infiltration in chronic limb-threatening ischemia.
Mitochondrial Complex I and ROS control neuromuscular function through opposing pre- and postsynaptic mechanisms.
Quality of life and disability 16 months after critical care illness: Comparison between COVID-19 and non-COVID-19 survivors.
Co-occurrence of Whole-body Muscle Wasting and Respiratory Muscle Weakness Affecting the Clinical Characteristics of Patients with Chronic Obstructive Pulmonary Disease.
A subclass of small RNAs is encoded by exons of protein-coding genes.

bioRxiv. 2025 Sep 17. pii: 2025.09.15.676415. [Epub ahead of print]

Fiber-type vulnerability and proteostasis reprogramming in skeletal muscle during pancreatic cancer cachexia.

Bowen Xu, Aniket S Joshi, Meiricris Tomaz da Silva, Silin Liu, Ashok Kumar.

Cachexia is a debilitating syndrome marked by progressive skeletal muscle wasting, commonly affecting cancer patients, particularly those with pancreatic cancer. Despite its clinical significance, the molecular mechanisms underlying cancer cachexia remain poorly understood. In this study, we utilized single-nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq, complemented by biochemical and histological analyses, to investigate molecular alterations in the skeletal muscle of the KPC mouse model of pancreatic cancer cachexia. Our findings demonstrate that KPC tumor growth induces myofiber-specific changes in the expression of genes involved in proteolytic pathways, mitochondrial biogenesis, and angiogenesis. Notably, tumor progression enhances the activity of specific transcription factors that regulate the mTORC1 signaling pathway, along with genes involved in translational initiation and ribosome biogenesis. Skeletal muscle-specific, inducible inhibition of mTORC1 activity further exacerbates muscle loss in tumor-bearing mice, highlighting its protective role in maintaining muscle mass. Additionally, we uncovered novel intercellular signaling networks within the skeletal muscle microenvironment during pancreatic cancer-induced cachexia. Together, these results reveal previously unrecognized molecular mechanisms that regulate skeletal muscle homeostasis and identify potential therapeutic targets for the treatment of pancreatic cancer-associated cachexia.

DOI: https://doi.org/10.1101/2025.09.15.676415
Proc Natl Acad Sci U S A. 2025 Sep 30. 122(39): e2424246122

The multimodal transcriptional response of denervated skeletal muscle involves regulation of Gramd1 genes impacting muscle size.

Cristofer Calvo, Casey O Swoboda, Fabian Montecino-Morales, Siddhant Nagar, Michael J Petrany, Chengyi Sun, Hima Bindu Durumutla, Mattia Quattrocelli, Douglas P Millay.

  The development and maintenance of the neuromuscular junction (NMJ) requires reciprocal signals between the nerve terminals and multinucleated skeletal muscle fibers (myofibers). This interaction drives highly specialized transcription in the subsynaptic or NMJ myonuclei within mature myofibers leading to clustering of acetylcholine receptors (AChRs). Here, we utilized single-nucleus RNA sequencing (snRNA-seq) to delineate the transcriptional response of myonuclei to denervation. Through snRNA-seq on skeletal muscle from two independent mouse models of denervation, sciatic nerve transection and amyotrophic lateral sclerosis, we identify a multimodal transcriptional response of NMJ-enriched genes and an alteration in cholesterol homeostasis in myofibers. Gramd1, a family of genes involved in nonvesicular cholesterol transport, are enriched at the NMJ in innervated muscle and upregulated in both models of denervation by the NMJ and extrasynaptic myonuclei. In vivo gain and loss of function studies indicate that Gramd1 genes regulate myofiber sizes. Mechanistically, we did not detect obvious changes in AChR clustering due to Gramd1 knockdown but revealed a role in autophagy after denervation. We uncovered a dynamic transcriptional response of myonuclei to denervation and highlight a critical role for Gramd1 to maintain myofiber sizes.

Keywords:  Gramd1b/Aster; cholesterol; neuromuscular synapse; snRNA sequencing

DOI:  https://doi.org/10.1073/pnas.2424246122
bioRxiv. 2025 Sep 18. pii: 2025.09.16.676620. [Epub ahead of print]

Hepatic ketogenic insufficiency blunts exercise-induced energy expenditure and alters mitochondrial proteins in skeletal muscle.

Xin C Davis, Colin S McCoin, Sebastian F Salathe, Edziu Franczak, Julie A Allen, Eric D Queathem, Kyle L Fulghum, Patrycja Puchalska, Peter A Crawford, John P Thyfault, E Matthew Morris.

Ketone body (KB) utilization increases during fasting and exercise due to enhanced hepatic fatty acid oxidation and KB production via the rate-limiting mitochondrial enzyme hydroxymethylglutaryl-CoA synthase (HMGCS2). Since KB metabolism intersects with multiple metabolic pathways, and skeletal muscle KB catabolism rises during exercise, we tested the hypothesis that liver-specific HMGCS2 knockouts (KO) would have reduced energy expenditure (EE) and changes in the mitochondrial proteome of skeletal muscle with chronic exercise through voluntary wheel running (VWR), time-restricted feeding (TRF), or both combined to boost hepatic KB production and utilization. Control (CON) and HMGCS2 knockout (KO) mice (n=6-8 per group) underwent sedentary ad libitum feeding (SED+AL), SED+TRF, VWR+AL, and VWR+TRF for 16 weeks, with whole-body EE measured using indirect calorimetry. In CON mice, VWR increased total EE by 19.5% and non-resting EE by 50% under AL conditions, and total EE by 16% and non-resting EE by 47.9% under TRF conditions. However, the EE increases seen with VWR did not occur in KO mice. Proteomic analysis revealed that the loss of liver HMGCS2 significantly impacted proteins involved in metabolic processes within skeletal muscle, including reduced oxidative phosphorylation (OXPHOS) protein expression in SED KO mice compared to sedentary CON. Notably, VWR restored OXPHOS protein expression in the muscle of the liver HMGCS2 KO but did not alter it in the CON. Furthermore, muscle from liver HMGCS2 KO mice had elevated expression glycolytic pathways in sedentary and VWR conditions. These results indicate that hepatic ketogenic deficiency (HMGCS2 KO) diminishes exercise-induced increases in EE and uniquely impacts baseline and exercise-related adaptations in the metabolic and mitochondrial proteome of skeletal muscle.

DOI: https://doi.org/10.1101/2025.09.16.676620
Am J Physiol Cell Physiol. 2025 Sep 22.

Isolation of functional lysosomes from skeletal muscle.

Thulasi Mahendran, Anastasiya Kuznyetsova, Neushaw Moradi, David A Hood.

  Lysosomes are membrane-bound organelles responsible for the degradation of damaged or dysfunctional cellular components, including mitochondria. Their acidic internal environment and the presence of an array of hydrolytic enzymes facilitate the efficient breakdown of macromolecules such as proteins, lipids, and nucleic acids. Mitochondria play a critical role in maintaining skeletal muscle homeostasis to meet the energy demands under physiological and pathological conditions. Mitochondrial quality control within skeletal muscle during processes such as exercise, disuse, and injury is regulated by mitophagy, where dysfunctional mitochondria are targeted for lysosomal degradation. The limited understanding of quality control mechanisms in skeletal muscle necessitates the need for isolating intact lysosomes to assess organelle integrity and the degradative functions of hydrolytic enzymes. Although several methods exist for lysosome isolation, the complex structure of skeletal muscle makes it challenging to obtain relatively pure and functional lysosomes due to the high abundance of contractile proteins. Here we describe a method to isolate functional lysosomes from small amounts of mouse skeletal muscle tissue, preserving membrane integrity. We also describe functional assays that allow direct evaluation of lysosomal enzymatic activity and we provide data indicating reduced lysosomal degradative activity in lysosomes from aging muscle. We hope that this protocol provides a valuable tool to advance our understanding of lysosomal biology in skeletal muscle, supporting investigations into lysosome-related dysfunction in aging, disease, and exercise adaptations.

Keywords:  differential centrifugation; lysosomal enzymes; mitochondria; mitophagy; proteolysis

DOI:  https://doi.org/10.1152/ajpcell.00471.2025
J Physiol. 2025 Sep 22.

Semaglutide impacts skeletal muscle to a similar extent as caloric restriction in mice with diet-induced obesity.

S Jeromson, B Baranowski, M Akcan, B D Waters, K Eisner, A Bellucci, S Trang, A Abolhassani, M A Tello-Palencia, A Schweitzer, B Stefanska, C J Mitchell, David C Wright.

  Semaglutide is a GLP-1 receptor agonist that is highly efficacious in reducing food intake and body weight. While semaglutide reduces adipose tissue, there is also a loss of lean mass including skeletal muscle, though it is unclear whether this translates to a loss of muscle function. The effect of discontinuation of semaglutide on rebound weight gain and shifts in body composition is also not well understood. We investigated the impact of semaglutide and matched caloric restriction on body composition in mice with diet-induced obesity. Mice were treated with semaglutide or fed a calorie-matched diet for 4 weeks. Semaglutide and pair-feeding induced significant weight loss with a concomitant reduction in energy expenditure. Weight loss was greater with semaglutide than caloric restriction, despite matched energy intake. Muscle transcriptomic analyses revealed distinct molecular responses between semaglutide and pair-feeding. In a follow-up experiment, semaglutide and pair-feeding was discontinued after 4 weeks, and body weight and food intake were tracked for 6 weeks. At the end of the withdrawal period there was a loss of treatment effects. Lean and fat mass rebounded to baseline levels at the end of the withdrawal period. Muscle size and strength were also comparable between groups. These findings demonstrate that semaglutide reduces muscle size and strength to the same extent as caloric restriction but may be more effective at promoting fat loss. Interestingly, the loss of lean mass and skeletal muscle recovered following treatment discontinuation. KEY POINTS: Semaglutide results in greater weight loss than caloric restriction. Semaglutide treatment increases fat loss compared with caloric restriction. Muscle mass and strength is reduced to a similar extent by semaglutide and restricted feeding.

Keywords:  obesity; semaglutide; skeletal muscle; weight loss

DOI:  https://doi.org/10.1113/JP289449
Sci Adv. 2025 Sep 26. 11(39): eadt6366

Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism.

Ashutosh Kumar, Yonghui Zhao, Litao Xie, Rahul Chadda, John D Tranter, Ryan T Mikami, Nihil Abraham, Juan Hong, Ethan Feng, David R Rawnsley, Haiyan Liu, Kayla M Henry, Gretchen Meyer, Meiqin Hu, Haoxing Xu, Antentor Hinton, Chad E Grueter, E Dale Abel, Andrew W Norris, Abhinav Diwan, Rajan Sah.

The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A knockout cells. In vivo, LRRC8A-L706A;L707A knock-in mice exhibit increased adiposity, impaired glucose tolerance and insulin resistance associated with reduced skeletal muscle PI3K-AKT-mTOR signaling, glucose uptake, and impaired incorporation of glucose into glycogen. These data reveal a lysosomal LRRC8-mediated metabolic signaling function regulating lysosomal function, systemic glucose homeostasis, and insulin sensitivity.

DOI: https://doi.org/10.1126/sciadv.adt6366
JVS Vasc Sci. 2025 ;6 100295

Vascular adhesion molecule 1+ fibro-adipogenic progenitors mark fatty infiltration in chronic limb-threatening ischemia.

Qunsheng Dai, Changxin Wan, Yueyuan Xu, Kaileen Fei, Lindsey A Olivere, Hana Shafique, Shaghayegh Sadeghmousavi, Camryn Johnson, Brianna Garrett, Leo Akers, Derek Peters, James Otto, Christopher D Kontos, Zhiceng Ji, Yarui Diao, Kevin W Southerland.

   Background: Skeletal muscle health and function are critical determinants of clinical outcomes in peripheral arterial disease. Chronic limb-threatening ischemia (CLTI), the most severe clinical manifestation of peripheral arterial disease, is associated with a 1-year amputation rate of 25%. In patients with CLTI, myosteatosis-the ectopic deposition of adipocytes-is independently associated with amputation. The mechanisms responsible for myosteatosis in patients with CLTI remain unknown. In this study, we aim to identify both the causal cellular population and the molecular mechanisms in patients with CLTI that promote myosteatosis.
Methods: To identify a candidate causal cell type and putative signaling axis that promotes myosteatosis, we performed single cell transcriptomic and chromatin accessibility profiling of ischemic muscle in a preclinical CLTI model. To assess the adipogenic potential for candidate subpopulations, we used an in vitro adipogenesis assay; myosteatosis was determined by Oil Red O (ORO), perilipin, and peroxisome proliferator-activated receptor gamma (PPAR-γ) staining. To determine the necessity of candidate transcriptional and epigenetic regulators, we used a small interfering RNA (siRNA). Finally, to assess the clinical significance of our findings, we used a publicly available human CLTI single cell RNA-sequencing dataset.
Results: Bulk-RNA sequencings and ORO staining reveal myosteatosis as a hallmark feature of the CLTI limb. Bioinformatic analyses reveal vascular adhesion molecule 1 (Vcam1)+ fibro-adipogenic progenitors (FAPs) to be a proadipogenic cluster. Vcam1+ FAPs display increased adipogenic potential compared with Vcam1- FAPs (ORO staining, P < .001; perilipin staining, P < .01; PPAR-γ staining, P < .05). Analyses of bulk and single cell RNA-sequencing datasets identify Sfrp1 as a regulator of Vcam1+ FAP adipogenic differentiation. In vitro inhibition of Sfrp1 with a siRNA demonstrated impaired Vcam1+ FAP adipogenic differentiation. Single cell ATAC sequencing identifies Nr3c1 as a candidate transcription factor that regulates Vcam1+ FAP adipogenic differentiation. In vitro inhibition of Nr3c1 with a siRNA demonstrated decreased Sfrp1 expression (P < .01) and impaired adipogenic differentiation (ORO staining, P < .01; perilipin staining, P < .05; PPAR-γ, P < .001). Single cell transcriptomic profiling of paired nonischemic and ischemic muscle specimens from patients with CLTI displayed enriched gene expression of Vcam1 (P = 5.24e-166; log2FC = 0.89), Sfrp1 (P = 0; log2FC = 1.49) and Nr3c1 (P = .047; log2FC = 0.050) in ischemic CLTI muscle tissues. Altogether, these data reveal a candidate signaling axis, Nr3c1-Sfrp1, that regulates the differentiation of Vcam1+ FAPs into adipocytes.
Conclusions: Collectively, our results identify a pro-adipogenic FAP subpopulation in patients with CLTI and provide a potential therapeutic target for myosteatosis in patients with CLTI.
Clinical Relevance: Myosteatosis, the pathological accumulation of fat within skeletal muscle, is increasingly recognized as a critical determinant of adverse clinical outcomes in peripheral arterial disease (PAD). Current therapies for PAD focus on revascularization and risk factor modification, but do not directly target myopathy. There is a critical need for regenerative and cellular therapies to restore muscle integrity and function. This study addresses this need by identifying a candidate causal cellular population, Vcam1+ fibroadipogenic progenitors, and a signaling axis, Nr3c1-Sfrp1, that promote myosteatosis in the ischemic limb.

Keywords:  Amputation; Chronic limb-threatening ischemia; Fibro-adipogenic progenitors; Myosteatosis; Peripheral arterial disease

DOI:  https://doi.org/10.1016/j.jvssci.2025.100295
PLoS Biol. 2025 Sep 22. 23(9): e3003388

Mitochondrial Complex I and ROS control neuromuscular function through opposing pre- and postsynaptic mechanisms.

Bhagaban Mallik, Sajad A Bhat, Xinnan Wang, C Andrew Frank.

Neurons require high amounts of energy, and mitochondria help to fulfill this requirement. Dysfunctional mitochondria trigger problems in various neuronal tasks. Using the Drosophila neuromuscular junction (NMJ) as a model synapse, we previously reported that Mitochondrial Complex I (MCI) subunits were required for maintaining NMJ function and growth. Here, we report tissue-specific adaptations at the NMJ when MCI is depleted. In Drosophila motor neurons, MCI depletion causes profound cytological defects and increased mitochondrial reactive oxygen species (ROS). But instead of diminishing synapse function, neuronal ROS triggers a homeostatic signaling process that maintains normal NMJ excitation. We identify molecules mediating this compensatory response. MCI depletion in muscles also enhances local ROS. But high levels of muscle ROS cause destructive responses: synapse degeneration, mitochondrial fragmentation, and impaired neurotransmission. In humans, mutations affecting MCI subunits cause severe neurological and neuromuscular diseases. The tissue-level effects that we describe in the Drosophila system are potentially relevant to forms of mitochondrial pathogenesis.

DOI: https://doi.org/10.1371/journal.pbio.3003388
Med Intensiva (Engl Ed). 2025 Sep 22. pii: S2173-5727(25)00183-3. [Epub ahead of print] 502309

Quality of life and disability 16 months after critical care illness: Comparison between COVID-19 and non-COVID-19 survivors.

Liliana Cristina da Silva Ferreira Fontes, Bárbara Peleteiro, Paulo Jorge Ribeiro Costa, Joana Carolina João Fernandes, Tatiana Santos Vieira, António José Falcão Braga, Sónia Patrícia Vilar Martins, Ana Rita Leal Ferreira, Isabel Maria Metelo Coimbra, Lia Paula Nogueira Sousa Fernandes, José Artur Osório de Carvalho Paiva.

   OBJECTIVE: Describe and compare the Quality of Life (QoL) and disability of critical care survivors with COVID-19 and NON-COVID-19 critical illness, admitted during and after the pandemic period. We hypothesize that both COVID-19 disease and the pandemic context have a significant impact on long-term outcomes of Intensive Care Unit (ICU) survivors.
DESIGN: Post-hoc analysis of prospectively collected data.
SETTING: Intensive Care Department of Unidade Local de Saúde São João between 1st October 2020 and 31st December 2021.
PARTICIPANTS: Three groups of adult critical care survivors; Group 1: critical COVID-19 patients; Group 2: critical patients with other diagnosis, admitted in the pandemic period; Group 3: critical patients admitted in the post-pandemic period due to non-COVID-19 causes.
INTERVENTION: Telephone consultation 16 months after discharge home, assessing QoL and disability.
MAIN VARIABLES OF INTEREST: QoL five dimensions, EuroQol Visual Analog Scale (EQ-VAS) and Health and disability 6 domains.
RESULTS: Of the 185 survivors, Group 1 reported less problems in"Self-care" (OR = 0.15, 95%CI: 0.04-0.55), "Usual activities" (OR = 0.20, 95%CI: 0.08-0.0.52), and "Anxiety/Depression" (OR = 0.36, 95%CI: 0.14-0.97) dimensions. Health and disability domains assessment showed Group 1 had less difficulties in "Cognition" (OR = 0.37, 95%CI: 0.15-0.91), "Mobility" (OR = 0.25, 95%CI: 0.09-0.68), "Self-care" (OR = 0.15, 95%CI: 0.05-0.40) and "Life activities" (OR = 0.32, 95%CI: 0.13-0.76).
CONCLUSIONS: Sixteen months after discharge home, survivors of non-COVID-19 admitted during the pandemic period present worse QoL and functional status than COVID-19 survivors admitted during the same period and greater post-hospital discharge healthcare needs.

Keywords:  COVID-19; Calidad de vida; Critical care; Cuidados críticos; Disability; Discapacidad; Follow-up; Quality of life; Seguimiento

DOI:  https://doi.org/10.1016/j.medine.2025.502309
Phys Ther Res. 2025 ;28(2): 145-149

Co-occurrence of Whole-body Muscle Wasting and Respiratory Muscle Weakness Affecting the Clinical Characteristics of Patients with Chronic Obstructive Pulmonary Disease.

Atsuyoshi Kawagoshi, Masahiro Iwakura, Yutaka Furukawa, Takeshi Kera, Hisashi Kawai, Shuichi Obuchi, Keiyu Sugawara, Takanobu Shioya.

   OBJECTIVES: The effect of the co-occurrence of whole-body muscle wasting and respiratory muscle weakness on the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated this association in patients with chronic respiratory diseases.
METHODS: 47 outpatients with mild to very severe COPD were classified into four groups according to their fat-free mass index and respiratory muscle strength: 19 without muscle wasting and respiratory muscle weakness (normal), 6 with muscle wasting only (MW), 11 with respiratory weakness only (RW), and 11 with muscle wasting and respiratory weakness (MW + RW). We measured their body composition, pulmonary function, lower muscle strength, submaximal exercise capacity, physical activity in daily life, nutritional status, frailty status, and health-related quality of life (QOL). Multiple linear regression analyses examined the association of muscle wasting and/or respiratory muscle weakness with participant characteristics, using each participant's characteristics as an explained variable adjusted for confounding variables (Normal as the reference).
RESULTS: The regression analysis revealed that the percentage of vital capacity, lower muscle strength, submaximal exercise capacity, nutritional status, and frailty status were worse in the MW + RW group than in the Normal group. The MR + RW group had the largest number of variables with significant differences compared to the Normal group.
CONCLUSIONS: These data suggest that the co-occurrence of whole-body muscle wasting and respiratory muscle weakness was significantly associated with deteriorating clinical characteristics in patients with COPD.

Keywords:  Chronic obstructive pulmonary disease; Muscle strength; Muscular atrophy; Respiratory muscles

DOI:  https://doi.org/10.1298/ptr.E10316
BMC Genomics. 2025 Sep 26. 26(1): 827

A subclass of small RNAs is encoded by exons of protein-coding genes.

Tyron Chang, Dustin C Hancks.

   BACKGROUND: Small RNAs regulate gene expression in species across the tree of life. miRNAs, which impact a variety of cellular and physiological processes ranging from development and stress adaptation to host defense, are one of the best characterized classes of small RNA. Many miRNAs are produced from longer non-coding transcripts generated from host genes via a series of RNA cleavage reactions. The location of a small RNA within a host gene can shape the processing of the mature small RNA. For example, a type of miRNAs derived from host gene intronic sequence, referred to as miRtrons, are Drosha-independent and reliant on splicing for biogenesis. Relatedly, processing of a small RNA from an exon of a protein-coding mRNA, in principle, may destabilize it and compromise translation of the host gene. Prior to extensive transcriptome analysis, informatics analyses identified six human miRNAs embedded in exons of protein-coding genes and experimental studies have characterized additional anecdotal examples. Still, whether protein-coding mRNAs encoding small RNAs represent an appreciable class of host genes given the now recognized complexity of the transcriptome is unclear.
RESULTS: Our analysis finds 201 small RNAs (118 human and 83 mouse) encoded by expressed exons of protein-coding genes (5'-UTR, CDS, 3'-UTR). Forty-six of these cases (29 human and 17 mouse) are also present in MirGeneDB which includes the most up-to-date miRNA classifications. Many of these small RNAs are poorly characterized with 96% of the protein-coding host gene relationships identified here not previously known. Furthermore, the identification of nearly fifty human and mouse small RNAs embedded within coding exons of canonical ORFs suggests that overlapping hybrid genes might be more common than previously appreciated in higher organisms. Expression analysis for a subset of these small RNAs indicates that many display differential expression across human tissues with the pattern correlating significantly with the expression of the candidate protein-coding host gene.
SIGNIFICANCE: Overall, our analysis suggests that the number of protein-coding transcripts serving as host genes is greater than previously recognized. Our small RNA host gene classifications may serve as a resource to shed new light on small RNA biology, specific host genes, and gene regulation.

Keywords:   miR-147b ; miR-6084 ; B2M; C15orf48; Host gene; MiRNA; NPC2; PINK1; Post-transcriptional gene regulation; Small RNA; ZAP

DOI:  https://doi.org/10.1186/s12864-025-11982-3