Gene Regulation Research Articles

Host genetic regulation of specific functional groups in the rumen microbiome of dairy cows: Implications for lactation trait

IntroductionRuminants play a pivotal role in our society by transforming non-consumable substances from industrial by-products and plant fibers into valuable resources such as meat and milk. This remarkable conversion ability is primarily attributed to the rumen microbiota, which is influenced by various factors, including diet, climate, and geographical location. In recent years, increasing research has shown that host factors (breed, genetic variation, etc.) also play vital roles in shaping rumen microbial composition and function in cattle. ObjectiveThis study aims to provide a theoretical basis and an opportunity for further investigating the regulation of lactation traits in dairy cows through host genetics and the interaction with the rumen microbiota. MethodTo investigate the interactions between host genotype, rumen microbiota, and animal phenotype, we curated and analyzed the dairy herd improvement (DHI) data, single nucleotide polymorphisms (SNPs) genotypes, and 16S rumen microbiota data from 1,169 Holstein dairy cows. Heritability and microbiability estimation, along with genome-wide association studies (GWAS) were performed to identify candidate microorganisms and host genetic loci. ResultWe identified thirty-one heritable taxa, whose functions were predominantly enriched in carbohydrate metabolism and energy metabolism. The genome-wide association study revealed that nine heritable bacteria were significantly associated with forty-three SNPs. Functional genes located within or near these SNPs were primarily associated with rumen epithelial development. Additionally, these nine heritable bacteria were primarily annotated as complex polysaccharide degraders and butyrate producers, such as Fibrobacter sp900143055 and Pseudoruminococcus massiliensis, which showed significant associations with milk yield and milk fat percentage. Compared to previous studies, we newly discovered the existence of a high heritability of Olsenella umbonate, Butyrivibrio hungatei, among others.

The constructed high-density genetic map helps to explore the genetic regulation of erucic acid, oleic acid, and linolenic acid contents in Brassica juncea

Rapeseed mustard (Brassica juncea L.) is the third most important oilseed crop in the world but the genetic mechanism underlying its massive phenotypic variation remains largely unexplored. In this study, specific length amplified fragment sequencing (SLAF-Seq) was used to resequence a population comprising 197 F8 recombinant inbred lines (RILs), derived from a cross between vegetable-type Qichi881 and oilseed-type YufengZC in B. juncea. In total, 438,895 high-quality SLAFs were discovered, of which 47,644 were polymorphic, and 3,887 of the polymorphic markers met the requirements for genetic map construction. The final map included 3,887 markers on 18 linkage groups and was 1,830.23 cM in length, with an average distance of 0.47 cM between adjacent markers. Using the newly constructed high-density genetic map, a total of 53 QTLs for erucic acid (EA), oleic acid (OA), and linolenic acid (LNA) were detected and integrated into 8 consensus QTLs with two for each of these traits. For each of these three traits, two candidate genes were cloned and sequence analyzed, indicating colocalization with their respective consensus QTLs. The co-dominant allele-specific markers for Bju.FAD3.A03 and Bju.FAD3.B07 were developed and showed co-localization with their consensus QTL and co-segregation with LNA content, further supporting the results of QTL mapping and bioinformatic analysis. The expression level for the cloned homologous genes was also identified, which was tightly correlated with the EA, OA and LNA contents of different lines. The results would facilitate the improvement of fatty acid traits and molecular breeding of B. juncea. More use of the high-density genetic map created in this study is also discussed.

Endocrine pathology in young rabbits with cystic fibrosis

BackgroundCystic fibrosis (CF) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the CF transmembrane conductance regulator gene. CF-related pancreatic lesions are known to cause exocrine dysfunctions such...

Unlocking Genome Editing: Advances and Obstacles in CRISPR/Cas Delivery Technologies

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats associated with protein 9) was first identified as a component of the bacterial adaptive immune system and subsequently engineered into a genome-editing tool. The key breakthrough in this field came with the realization that CRISPR/Cas9 could be used in mammalian cells to enable transformative genetic editing. This technology has since become a vital tool for various genetic manipulations, including gene knockouts, knock-in point mutations, and gene regulation at both transcriptional and post-transcriptional levels. CRISPR/Cas9 holds great potential in human medicine, particularly for curing genetic disorders. However, despite significant innovation and advancement in genome editing, the technology still possesses critical limitations, such as off-target effects, immunogenicity issues, ethical considerations, regulatory hurdles, and the need for efficient delivery methods. To overcome these obstacles, efforts have focused on creating more accurate and reliable Cas9 nucleases and exploring innovative delivery methods. Recently, functional biomaterials and synthetic carriers have shown great potential as effective delivery vehicles for CRISPR/Cas9 components. In this review, we attempt to provide a comprehensive survey of the existing CRISPR-Cas9 delivery strategies, including viral delivery, biomaterials-based delivery, synthetic carriers, and physical delivery techniques. We underscore the urgent need for effective delivery systems to fully unlock the power of CRISPR/Cas9 technology and realize a seamless transition from benchtop research to clinical applications.

A computational model for bacteriophage ϕX174 gene expression.

Bacteriophage ϕX174 has been widely used as a model organism to study fundamental processes in molecular biology. However, several aspects of ϕX174 gene regulation are not fully resolved. Here we construct a computational model for ϕX174 and use the model to study gene regulation during the phage infection cycle. We estimate the relative strengths of transcription regulatory elements (promoters and terminators) by fitting the model to transcriptomics data. We show that the specific arrangement of a promoter followed immediately by a terminator, which occurs naturally in the ϕX174 genome, poses a parameter identifiability problem for the model, since the activity of one element can be partially compensated for by the other. We also simulate ϕX174 gene expression with two additional, putative transcription regulatory elements that have been proposed in prior studies. We find that the activities of these putative elements are estimated to be weak, and that variation in ϕX174 transcript abundances can be adequately explained without them. Overall, our work demonstrates that ϕX174 gene regulation is well described by the canonical set of promoters and terminators widely used in the literature.

Identification of the m6A/m5C/m1A methylation modification genes in Alzheimer's disease based on bioinformatic analysis.

As a progressive neurodegenerative disease, the comprehensive understanding of the pathogenesis of Alzheimer's disease (AD) is yet to be clarified. Modifications in RNA, including m6A/m5C/m1A, affect the onset and progression of many diseases. Consequently, this study focuses on the role of methylation modification in the pathogenesis of AD. Three AD-related datasets, namely GSE33000, GSE122063, and GSE44770, were acquired from GEO. Differential analysis of m6A/m5C/m1A regulator genes was conducted. Applying a consensus clustering approach, distinct subtypes within AD were identified as per the expression patterns of relevant differentially expressed genes. Machine learning models were constructed to identify five significant genes from the best model. The analysis of hub gene-based drug regulatory networks and ceRNA regulatory networks was conducted by Cytoscape. In comparison to non-AD patients, 24 genes were identified as dysregulated in AD patients, and these genes were associated with various immunological characteristics. Two distinct clusters were successfully identified through consensus clustering, with cluster 2 demonstrating higher immune characteristics compared to cluster 1. The performance of four machine learning models was determined by conducting a receiver operating characteristic (ROC) analysis. The analysis revealed that the SVM model achieved the highest AUC value of 0.947. Five genes (YTHDF1, METTL3, DNMT1, DNMT3A, ALKBH1) were selected as the predicted genes. Finally, a hub gene-based Gene-Drug regulatory network and a ceRNA regulatory network were successfully developed. The findings offered fresh perspectives on the molecular patterns and immune mechanisms underlying AD, contributing valuable insights into our understanding of this complex neurodegenerative disorder.

Insights into the Epigenetic Basis of Plant Salt Tolerance.

The increasing salinity of agricultural lands highlights the urgent need to improve salt tolerance in crops, a critical factor for ensuring food security. Epigenetic mechanisms are pivotal in plant adaptation to salt stress. This review elucidates the complex roles of DNA methylation, histone modifications, histone variants, and non-coding RNAs in the fine-tuning of gene expression in response to salt stress. It emphasizes how heritable changes, which do not alter the DNA sequence but significantly impact plant phenotype, contribute to this adaptation. DNA methylation is notably prevalent under high-salinity conditions and is associated with changes in gene expression that enhance plant resilience to salt. Modifications in histones, including both methylation and acetylation, are directly linked to the regulation of salt-tolerance genes. The presence of histone variants, such as H2A.Z, is altered under salt stress, promoting plant adaptation to high-salinity environments. Additionally, non-coding RNAs, such as miRNAs and lncRNAs, contribute to the intricate gene regulatory network under salt stress. This review also underscores the importance of understanding these epigenetic changes in developing plant stress memory and enhancing stress tolerance.

Integrin α6β4 Upregulates PTPRZ1 Through UCHL1-Mediated Hif-1α Nuclear Accumulation to Promote Triple-Negative Breast Cancer Cell Invasive Properties.

Integrin α6β4 drives triple-negative breast cancer (TNBC) aggressiveness through the transcriptional regulation of key genes. Here, we investigated how integrin α6β4 regulates protein tyrosine phosphatase receptor type Z1 (PTPRZ1). Using stable re-expression of integrin β4 (ITGB4) in cells naturally devoid of integrin α6β4 or knockdown or knockout (KO) of ITGB4, we found that integrin α6β4 regulates PTPRZ1 expression. To gain mechanistic insight, we focused on Hif-1α due to the impact of integrin α6β4 on a hypoxia-associated signature. We found that nuclear localization of Hif-1α, but not Hif-2α, was substantially enhanced with integrin α6β4 signaling. Hif-1α knockdown by shRNA or chemical inhibition decreased PTPRZ1 expression, while chemical activation of Hif-1α increased it. Upstream of Hif-1α, integrin α6β4 upregulates UCHL1 to stabilize Hif-1α and ultimately regulate PTPRZ1. Inhibition of UCHL1 and PTPRZ1 dramatically decreases integrin α6β4-mediated cell migration and three-dimensional invasive growth. Finally, public breast cancer database analyses demonstrated that ITGB4 correlates with PTPRZ1 and that high expression of ITGB4, UCHL1, HIF1A, and PTPRZ1 associated with decreased overall survival, distant metastasis free survival, post progression survival, and relapse-free survival. In summary, these findings provide a novel function of integrin α6β4 in promoting tumor invasive phenotypes through UCHL1-Hif-1α-mediated regulation of PTPRZ1.

The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State.

Lipid droplets are fat storage organelles composed of a protein envelope and lipid-rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all-trans-retinal to all-trans-retinol, is upregulated in the MITFLO/undifferentiated/neural crest-like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid-mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling.

Comparative Genomics Reveal Distinct Environment Preference and Functional Adaptation Among Lineages of Gemmatimonadota

Bacteria in the phylum Gemmatimonadota are globally distributed and abundant in microbial communities of various environments, playing an important role in driving biogeochemical cycling on Earth. Although high diversities in taxonomic composition and metabolic capabilities have been reported, little is known about the environmental preferences and associated functional features that facilitate adaptation among different Gemmatimonadota lineages. This study systematically analyzed the relationships between the environments, taxonomy, and functions of Gemmatimonadota lineages, by using a comparative genomics approach based on 1356 Gemmatimonadota genomes (213 high-quality and non-redundant genomes) available in a public database (NCBI). The taxonomic analysis showed that the 99.5% of the genomes belong to the class Gemmatimonadetes, and the rest of the genomes belong to the class Glassbacteria. Functional profiling revealed clear environmental preference among different lineages of Gemmatimonadota, and a marine group and two non-marine groups were identified and tested to be significantly different in functional composition. Further annotation and statistical comparison revealed a large number of functional genes (e.g., amiE, coxS, yfbK) that were significantly enriched in genomes from the marine group, supporting enhanced capabilities in energy acquisition, genetic information regulation (e.g., DNA repair), electrolyte homeostasis, and growth rate control. These genomic features are important for their survival in the marine environment, which is oligotrophic, variable, and with high salinity. The findings enhanced our understanding of the metabolic processes and environmental adaptation of Gemmatimonadota, and further advanced the understanding of the interactions of microorganisms and their habitats.

The Effect of Long-Term Physical Disability and Aging on Extracellular Matrix Biogenesis in Human Skeletal Muscle

Physical inactivity and aging cause significant impairments in the functionality and mechanical properties of skeletal muscles, as well as remodeling of the extracellular matrix (ECM). We aimed to study the effect of long-term inactivity and age on the biogenesis of ECM in skeletal muscle. For quantitative mass spectrometry-based proteomic analysis and RNA sequencing, biopsy samples were taken from m. vastus lateralis in 15 young healthy volunteers, 8 young and 37 elderly patients with long-term primary osteoarthritis of the knee/hip joint – which is a model for studying the effects of inactivity on muscles. We detected 1022 mRNAs and 101 ECM and associated proteins (matrisome). An increase in the expression of two dozen highly abundant matrisome proteins, specific to elderly and young patients (in relation to young healthy people), was detected; however, changes in the expression of mRNA encoding matrisome regulators (enzymatic regulators and secreted proteins) were similar. Comparison with previous proteomic and transcriptomic data showed that the changes in the matrisome that we described differed markedly from the changes caused by aerobic physical training in young healthy people, in particular, in the expression of the dominant ECM proteins and, especially, in the expression of mRNA of ECM enzymatic regulators and secreted proteins. Comparison of the changes in the expression profiles of these regulatory genes may be useful for identifying pharmacological targets for the prevention of adverse changes/activation of ECM biogenesis under various pathological conditions/physical training.

DNA methylation and non-coding RNAs in metabolic disorders: Epigenetic Roles of Nutrients, Dietary Patterns and Weight Loss Interventions for Precision Nutrition.

Dysregulation of epigenetic processes and abnormal epigenetic profiles are associated with various metabolic disorders. Nutrition, as an environmental factor, can induce epigenetic changes through both direct exposure and transgenerational inheritance, continuously altering gene expression and shaping the phenotype. Nutrients consumed through food or supplementation, such as vitamin B12, folate, vitamin B6, and choline, play a pivotal role in DNA methylation, a critical process for gene regulation. Additionally, there is mounting evidence that the expression of non-coding RNAs (ncRNAs) can be modulated by the intake of specific nutrients and natural compounds, thereby influencing processes involved in the onset and progression of metabolic diseases. Evidence suggests that dietary patterns, weight-loss interventions, nutrients and nutritional bioactive compounds can modulate the expression of various miRNAs and DNA methylation levels, contributing to development of metabolic disorders such as obesity and type 2 diabetes. Furthermore, several studies have proposed that DNA methylation and microRNA (miRNA) expression could serve as biomarkers for the effects of weight-loss programs. Despite ongoing debate regarding the effects of nutrient supplementation on DNA methylation levels and the expression of ncRNAs, certain DNA methylation marks and ncRNA expressions might predict the risk of metabolic disorders and act as biomarkers for forecasting the success of therapies within the framework of precision medicine and nutrition. The role of DNA methylation and miRNA expression as potential mediators of the effects of weight loss underscores their potential as biomarkers for the outcomes of weight loss programs. This highlights the influence of dietary patterns and weight-loss interventions on the regulation of miRNA expression and DNA methylation levels, suggesting an interaction between these epigenetic factors and the body's response to weight loss.

Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.

Across biological systems, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. While low-dimensional dynamics can be extracted using RNA velocity, these algorithms can be fragile and rely on heuristics lacking statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. To address these challenges, we introduce a Bayesian model of RNA velocity that couples velocity field and manifold estimation in a reformulated, unified framework, identifying the parameters of an explicit dynamical system. Focusing on the cell cycle, we implement VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validate its ability to infer cell cycle periods using live imaging. We also apply VeloCycle to reveal speed differences in regionally defined progenitors and Perturb-seq gene knockdowns. Overall, VeloCycle expands the single-cell RNA sequencing analysis toolkit with a modular and statistically consistent RNA velocity inference framework.

Global loss of promoter-enhancer connectivity and rebalancing of gene expression during early colorectal cancer carcinogenesis.

Although three-dimensional (3D) genome architecture is crucial for gene regulation, its role in disease remains elusive. We traced the evolution and malignant transformation of colorectal cancer (CRC) by generating high-resolution chromatin conformation maps of 33 colon samples spanning different stages of early neoplastic growth in persons with familial adenomatous polyposis (FAP). Our analysis revealed a substantial progressive loss of genome-wide cis-regulatory connectivity at early malignancy stages, correlating with nonlinear gene regulation effects. Genes with high promoter-enhancer (P-E) connectivity in unaffected mucosa were not linked to elevated baseline expression but tended to be upregulated in advanced stages. Inhibiting highly connected promoters preferentially represses gene expression in CRC cells compared to normal colonic epithelial cells. Our results suggest a two-phase model whereby neoplastic transformation reduces P-E connectivity from a redundant state to a rate-limiting one for transcriptional levels, highlighting the intricate interplay between 3D genome architecture and gene regulation during early CRC progression.

Description Generation Using Variational Auto-Encoders for Precursor microRNA

Micro RNAs (miRNA) are a type of non-coding RNA involved in gene regulation and can be associated with diseases such as cancer, cardiovascular, and neurological diseases. As such, identifying the entire genome of miRNA can be of great relevance. Since experimental methods for novel precursor miRNA (pre-miRNA) detection are complex and expensive, computational detection using Machine Learning (ML) could be useful. Existing ML methods are often complex black boxes that do not create an interpretable structural description of pre-miRNA. In this paper, we propose a novel framework that makes use of generative modeling through Variational Auto-Encoders to uncover the generative factors of pre-miRNA. After training the VAE, the pre-miRNA description is developed using a decision tree on the lower dimensional latent space. Applying the framework to miRNA classification, we obtain a high reconstruction and classification performance while also developing an accurate miRNA description.

The CRISPR-dCas9 interference system suppresses inhA gene expression in Mycobacterium smegmatis

CRISPR-dead Cas9 interference (CRISPRi) has become a valuable tool for precise gene regulation. In this study, CRISPRi was designed to target the inhA gene of Mycobacterium smegmatis (Msm), a gene necessary for mycolic acid synthesis. Our findings revealed that sgRNA2 induced with 100 ng/ml aTc achieved over 90% downregulation of inhA gene expression and inhibited bacterial viability by approximately 1,000-fold. Furthermore, CRISPRi enhanced the susceptibility of M. smegmatis to isoniazid and rifampicin, which are both 50% and 90% lower than those of the wild-type strain or other strains, respectively. This study highlights the ability of CRISPRi to silence the inhA gene, which impacts bacterial viability and drug susceptibility. The findings provide valuable insights into the utility of CRISPRi as an alternative tool for gene regulation. CRISPRi might be further assessed for its synergistic effect with current anti-tuberculosis drugs and its possible implications for combating mycobacterial infections, especially drug-resistant tuberculosis.

Polydeoxyribonucleotide ameliorates IL-1β-induced impairment of chondrogenic differentiation in human bone marrow-derived mesenchymal stem cells

Osteoarthritis (OA) is a degenerative disease of the joints, prevalent worldwide. Polydeoxyribonucleotide (PDRN) is used for treating knee OA. However, the role of PDRN in IL-1β-induced inflammatory responses in human bone marrow-derived mesenchymal stem cells (hBMSCs) remains unknown. Here, we investigated the role of PDRN in IL-1β-induced impairment of chondrogenic differentiation in hBMSCs. hBMSCs treated with PDRN showed a large micromass, enhanced safranin O and alcian blue staining intensity, and increased expression of chondrogenic genes in IL-1β-induced inflammatory responses, in addition to regulation of catabolic and anabolic genes. In addition, PDRN treatment suppressed the expression of inflammatory cytokines and mitigated IL-1β-induced apoptosis in hBMSCs. Mechanistically, PDRN treatment increased the formation of cyclic adenosine monophosphate (cAMP) and upregulated the phosphorylation of cAMP-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) through the adenosine A2A receptor in hBMSCs and thus blocked the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Thus, IL-1β-induced expression of inflammatory cytokines in hBMSCs was directly reduced by adenosine A2A receptor activation. Based on our results, we suggest that PDRN may be a promising MSC-based therapeutic agent for OA.

MiRNA Expression in Long-Distance Runners with Musculoskeletal Pain: Implications for Pain Pathophysiology

Background: miRNAs are short, non-coding RNAs whose deregulation has been shown in painful processes, including musculoskeletal pain. This condition, which causes disability, impacts quality of life, and contributes to substantial healthcare costs, is also a critical issue in sports. In this case-control study, we evaluated the expression of four miRNAs involved in inflammation in runners with musculoskeletal pain and elucidated their functions and pathophysiological implications. Methods: A total of 17 runners with musculoskeletal pain and 17 age- and sex-matched runners without pain participated in this study. The levels of the miRNAs were evaluated by qRT-PCR. Bioinformatic tools were employed to identify the target genes and biological processes regulated by these miRNAs. Results: Compared to the controls, the runners with musculoskeletal pain exhibited significantly higher plasma levels of miR-133b (p = 0.02), miR-155-5p (p = 0.003) and let-7a-5p (p = 0.02). Multivariable regression analysis indicated that these three miRNAs exhibit a positive correlation (p < 0.05) with the presence of musculoskeletal pain, adjusted for age. Bioinformatic analysis suggested that the miRNAs hub genes are involved in regulatory processes, neuroinflammatory pathways, and human diseases that are associated with pain pathology. Conclusions: These results enhance our understanding of the potential role of miR-133b, miR-155-5p and let-7a-5p in pain-associated biological processes. The miRNA-mediated negative regulation of genes identified could explain the inflammatory and tissue repair processes in this population. Further studies are needed to confirm and validate the role of these miRNAs in painful conditions, especially considering the significant public health implications of managing inflammatory pain in sports.

Investigating the Role of OsHDT701 and Other Blast-Associated Negative Regulatory Genes in Indica Rice Cultivar Ranjit Using Combined Wet Lab and Computational Approaches.

Rice blast, caused by Magnaporthe oryzae, severely impacts global rice production. Understanding the role of the host's blast negative regulatory genes is crucial for combating this disease. We studied the expression of seven rice blast negative regulatory genes (previously characterized in ssp. japonica) in susceptible (Ranjit and Mahsuri) and tolerant/resistant (Shahsarang 1 and IR64) indica rice cultivars during M. oryzae infection. The selected genes showed differential expression patterns, with OsHDT701 (histone H4 deacetylase) downregulated in tolerant/resistant and upregulated in susceptible cultivars. Promoter analysis of OsHDT701 in cv. Ranjit revealed biotic stress-responsive and M. oryzae effector binding motifs (MoHTR2 and MoSPAB1). Protein-DNA docking showed an interaction for both the effectors and promoter sequences. Furthermore, a strong interaction between the OsERF922 transcription factor (a negative regulator of rice blast) and GCC box at the promoter suggests OsERF922-mediated regulation of OsHDT701. Next, a comparative analysis of ssp. japonica (Nipponbare) OsHDT701 CDS to 11 indica rice cultivars, including Ranjit, detected an SNP (T-A) at position 591. Moreover, the structure modeling and protein-protein interaction reveal that OsHDT701 may form a complex with other histone deacetylases to regulate defense-related gene expression. Taken together, our study unveils new possibilities for OsHDT701 regulation mechanisms during M. oryzae infection.

Genome-wide analysis of non-coding RNA reveals the role of a novel miR319c for tuber dormancy release process in potato

Abstract Tuber dormancy and sprouting are significant for potato cultivation, storage, and processing. Although the substantial role of miRNAs in some biological processes has been recognized, the critical role of miRNA in breaking potato tuber dormancy is not well understood to date. In this investigation, we expand research on miRNA-mediated gene regulation in tuber dormancy release. In this work, 204 known and 192 novel miRNAs were identified. 136 differentially expressed miRNAs (DE-miRNAs) were also screened out, of which 56 DE-miRNAs were regulated by temperature during tuber dormancy release. Additionally, degradome sequencing revealed that 821 target genes for 202 miRNAs were discovered. Among them, 63 target genes and 48 miRNAs were predicted to be involved in plant hormone signaling pathways. This study used degradome sequencing, tobacco co-transformation system, and GUS staining technology to confirm that stu-miR319c can target StTCP26 and StTCP27 and effectively suppress their expression. The transgenic approach exhibited that stu-miR319c overexpressed tubers sprouted in advance, while silent expression of stu-miR319c showed delayed sprouting. Treatment of wild-type tubers with exogenous MeJA revealed that 1 mg/L MeJA significantly broke dormancy and enhanced potato sprouting ability. Furthermore, transgenic tubers revealed variance in JA content and relative expression of genes associated with JA synthesis pathway, including StAOC, StLOX2, and StLOX4, suggesting that the miR319c may participate in the JA pathway to regulate tuber dormancy release. In summary, our research offers evidence that miRNA regulates potato dormancy release and supports the idea that stu-miR319c is a unique epigenetic regulator for dormancy-sprouting transition in potatoes.