{"title":"Effect of sugar modifications on the solution stability of nucleoside phosphoramidites.","authors":"Kosuke Chiba, Junsuke Hayashi, Ryohei Kajino, Tsuyoshi Maekawa, Tadashi Umemoto, Junji Kawakami, Takao Inoue, Satoshi Obika, Takashi Osawa, Ajaya Ram Shrestha","doi":"10.1080/15257770.2026.2722681","DOIUrl":"https://doi.org/10.1080/15257770.2026.2722681","url":null,"abstract":"<p><p>Oligonucleotide therapeutics represent a rapidly advancing class of medicines that has attracted substantial attention in recent years. Phosphoramidites with chemical modifications are essential building blocks for their chemical synthesis. Therefore, a deep understanding about the stability of phosphoramidites is crucial for the manufacturing of oligonucleotide therapeutics. Especially, it is known that the DNA phosphoramidite with isobutyryl protected-guanine nucleobase (dG[iBu]) is unstable in anhydrous solution. In this study, the solution stabilities of dG[iBu] phosphoramidites with sugar modification were evaluated. The sugar-modified phosphoramidites in acetonitrile were found to be more stable than DNA phosphoramidites, probably due to steric hindrance of the modifications at their 2'-position. Moreover, <i>N</i>,<i>N</i>-dimethylformamide and dichloromethane were identified as alternative solvents that could improve stability without affecting the reactivity of phosphoramidites in oligonucleotide synthesis.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-13"},"PeriodicalIF":1.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leysan R Safargalieva, Bulat F Garifullin, Ravil F Aznagulov, Alexandra D Voloshina, Anna P Lyubina, Olga V Andreeva, Mayya G Belenok, Radmila R Sharipova, Marina M Shulaeva, Liliya F Saifina, Vyacheslav E Semenov, Vladimir E Kataev
{"title":"Synthesis, cytotoxicity, and antimicrobial activity of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of pyrimidine nucleosides bearing <i>N</i>-acetyl-β-D-glucosamine residue.","authors":"Leysan R Safargalieva, Bulat F Garifullin, Ravil F Aznagulov, Alexandra D Voloshina, Anna P Lyubina, Olga V Andreeva, Mayya G Belenok, Radmila R Sharipova, Marina M Shulaeva, Liliya F Saifina, Vyacheslav E Semenov, Vladimir E Kataev","doi":"10.1080/15257770.2026.2718121","DOIUrl":"https://doi.org/10.1080/15257770.2026.2718121","url":null,"abstract":"<p><p>A series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of pyrimidine nucleosides was synthesized. In these compounds a TPP cation was attached <i>via</i> a decamethylene linker to the atom <i>N</i>-3 of the nucleic base (uracil, thymine) or its analog (6-methyluracil), and the <i>N</i>-acetyl-β-D-glucosamine residue with protected (or unprotected) hydroxyl groups was attached <i>via</i> a 1,2,3-triazolylmethyl or 1,2,3-triazolylbutyl linker to the atom <i>N</i>-1 of the listed pyrimidine derivatives. All synthesized TPP-conjugates caused the death of MCF-7 cancer cells within the range IC<sub>50</sub> = 1.9-27 µM and PC-3 cancer cells within the range IC<sub>50</sub> = 2.6-19.4 µM. Bacteriostatic and bactericidal activity against Gram-positive bacteria <i>Staphylococcus aureus</i>, <i>Bacillus cereus</i>, and methicillin-resistant strains of <i>S. aureus</i> MRSA-1 and MRSA-2 was detected for several TPP-conjugates within the concentration range (MIC and MBC) from 7.8 to 15.6 µM.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-31"},"PeriodicalIF":1.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Study on the role of miR-433-3p in the occurrence and development of endometriosis.","authors":"Lulu Wang, Jing Bai, Xiaoqing Zhu","doi":"10.1080/15257770.2026.2718818","DOIUrl":"https://doi.org/10.1080/15257770.2026.2718818","url":null,"abstract":"<p><p>This study aims to characterize the expression pattern and biological functions of miR-433-3p in endometriosis. Eutopic and ectopic endometrial tissues were collected from endometriosis patients, and the expression level of miR-433-3p was detected by RT-qPCR. Serum samples were also collected from endometriosis patients and healthy female controls, and the diagnostic value of miR-433-3p for endometriosis was evaluated by receiver operating characteristic curve. In cell experiments, CCK-8 and Transwell assays were performed to assess the effects of miR-433-3p on the proliferation, migration and invasion of endometrial stromal cells (ESCs). RT-qPCR was used to detect the expression levels of epithelial-mesenchymal transition (EMT) markers. A dual-luciferase reporter assay was conducted to verify the targeted binding relationship between miR-433-3p and CHL1. The results showed that the level of miR-433-3p in ectopic endometrium was significantly lower than that in eutopic endometrium. Moreover, circulating miR-433-3p levels in the serum of endometriosis patients were significantly lower than those in healthy controls. Serum miR-433-3p demonstrated excellent diagnostic efficacy for endometriosis, with an AUC of 0.8777, a sensitivity of 93.90%, and a specificity of 76.25%. In cells, overexpression of miR-433-3p significantly suppressed the proliferation, migration, invasion and EMT. Mechanistically, CHL1 was identified as a direct downstream target of miR-433-3p, and rescue experiments confirmed that restored CHL1 expression could partially reverse the inhibitory effect of miR-433-3p on the aggressive biological phenotype of ESCs. Based on the above research results, we propose the following hypothesis: In endometriosis, miR-433-3p may inhibit the proliferation and invasion of ESCs by targeting CHL1. Moreover, circulating miR-433-3p is expected to become a non-invasive candidate biomarker for endometriosis.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-16"},"PeriodicalIF":1.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huinan Zhao, Qiang Fu, Wen Gong, Miao Yu, Huixuan Li
{"title":"LncRNA APTR as a potential prognostic biomarker for triple-negative breast cancer.","authors":"Huinan Zhao, Qiang Fu, Wen Gong, Miao Yu, Huixuan Li","doi":"10.1080/15257770.2026.2710129","DOIUrl":"https://doi.org/10.1080/15257770.2026.2710129","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is the most invasive subtype of breast cancer (BC) with high recurrence, high mortality, poor prognosis, and a lack of effective targeted therapies. This study aimed to investigate the prognostic value of lncRNA Alu-mediated p21 transcriptional regulator (APTR) in TNBC. APTR/miR-298 levels in TNBC tissues and cell lines were detected by RT-qPCR. The correlation between APTR and the prognosis of TNBC patients was analyzed by Kaplan-Meier survival analysis. The direct binding relationship between APTR and miR-298 was verified with a luciferase reporter assay. CCK-8 and Transwell assays were conducted to elucidate the role of APTR knockdown and miR-298 co-knockdown in regulating the viability and migration of TNBC cells. APTR was upregulated in TNBC tissues and cell lines, while miR-298 was downregulated. High APTR expression was closed associated with poor prognosis of TNBC patients. Mechanistically, APTR directly binds to and negatively regulates miR-298. Functional experiments showed that knockdown of APTR significantly inhibited the viability and migration of TNBC cells, while miR-298 inhibition partially abrogated these tumor-suppressive effects. APTR is upregulated in TNBC and is closely related to poor prognosis. APTR exerts an oncogenic role in TNBC by negatively regulating miR-298, suggesting that APTR serves as a promising novel prognostic biomarker for TNBC.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-14"},"PeriodicalIF":1.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cation- and sequence length-dependent kinetics for B-/Z-DNA transition.","authors":"Jesse Vanloon, Hongbin Yan","doi":"10.1080/15257770.2026.2718122","DOIUrl":"https://doi.org/10.1080/15257770.2026.2718122","url":null,"abstract":"<p><p>This work examined the kinetics for the B→Z-DNA transition of tandem d(CG) repeat sequences induced by NaCl, KCl, MgCl<sub>2</sub>, and spermine. While d(CG)<sub>3</sub> undergoes an incomplete transition, d(CG)<sub>6</sub>, d(CG)<sub>9</sub>, and d(CG)<sub>18</sub> transition fully in appropriate concentrations of salts or spermine. The transition proceeds more slowly with increasing DNA lengths. Furthermore, d(CG)<sub>18</sub> displays complex behavior in the presence of MgCl<sub>2</sub>. While d(CG)<sub>18</sub> fully transitions to Z-DNA in the presence of 2.5 <i>M</i> MgCl<sub>2</sub>, the process is complicated, likely by condensation. Kinetics of the B-/Z-DNA transition is an important aspect of Z-DNA's roles in biological systems. The knowledge of how this transition is affected by sequence lengths and salts helps define the DNA's conformational plasticity in response to environmental shifts in cells.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-11"},"PeriodicalIF":1.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olga V Andreeva, Bulat F Garifullin, Alexandra D Voloshina, Anna P Lyubina, Mayya G Belenok, Radmila R Sharipova, Ravil F Aznagulov, Liliya F Saifina, Marina M Shulaeva, Vyacheslav E Semenov, Vladimir E Kataev
{"title":"Nucleoterpenoids consisting of isosteviol and uridine. Synthesis and cytotoxicity evaluation.","authors":"Olga V Andreeva, Bulat F Garifullin, Alexandra D Voloshina, Anna P Lyubina, Mayya G Belenok, Radmila R Sharipova, Ravil F Aznagulov, Liliya F Saifina, Marina M Shulaeva, Vyacheslav E Semenov, Vladimir E Kataev","doi":"10.1080/15257770.2026.2710132","DOIUrl":"https://doi.org/10.1080/15257770.2026.2710132","url":null,"abstract":"<p><p>A series of nucleoterpenoids in which uridine is attached to diterpenoid isosteviol (16-oxo-<i>ent</i>-beyeran-19-oic acid) by means of an alkyl or 1,2,3-triazolylalkyl linker has been synthesized. Screening of their <i>in vitro</i> cytotoxicity against 7 cancer cell lines revealed three lead compounds. This is nucleoterpenoid <b>13c</b> in which the uridine moiety is attached by the octyl linker to the amide group of isosteviol. Compound <b>13c</b> caused the death of MCF-7 and PANC-1 cancer cells at an IC<sub>50</sub> concentration of 11 µM. Nucleoterpenoid <b>15b</b>, in which the uridine moiety with protected hydroxyl groups is attached by the 1,2,3-triazolylbutyl linker to the C-16(<i>S</i>) position of isosteviol, caused the death of cancer cells M-HeLa, MCF-7, PANC-1, PC-3, A 549, and HuTu 80 at IC<sub>50</sub> values in the range 10.4-16.8 µM. Its derivative, nucleoterpenoid <b>15d</b> with free hydroxyl groups, caused the death of cancer cells MCF-7, PANC-1, PC-3, and A 549 at IC<sub>50</sub> values in the range 11.7-19.5 µM.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-32"},"PeriodicalIF":1.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A K Smitha, V Srinivasa Murthy, M Sennappan, B Vinay Kumar, A H Shridhar, Lohit Naik, K Ravi Kumar, K Yogendra, N Madhusudhana
{"title":"Synergistic MgSiO<sub>3</sub> nanocatalysis for the efficient synthesis of benzo[<i>d</i>]oxazol-2-yl phenylisoxazoles: structural elucidation, drug-likeness profiling, and target-oriented biomolecular interactions.","authors":"A K Smitha, V Srinivasa Murthy, M Sennappan, B Vinay Kumar, A H Shridhar, Lohit Naik, K Ravi Kumar, K Yogendra, N Madhusudhana","doi":"10.1080/15257770.2026.2705884","DOIUrl":"https://doi.org/10.1080/15257770.2026.2705884","url":null,"abstract":"<p><p>A new library of 2-(5-phenylisoxazole-3-yl)benzo[<i>d</i>]oxazole derivatives <b>3(a-f)</b> was synthesized through a magnesium silicate nanocatalyst-assisted condensation of 2-aminophenol with a series of substituted 5-phenylisoxazole-3-carbaldehydes. The identity of the products was confirmed by FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and mass spectrometry. Their interaction with calf thymus DNA (CT-DNA) was systematically examined using absorption spectroscopy, viscosity assays, thermal denaturation experiments, and molecular docking simulations. The compounds exhibited binding constants in the 10<sup>5</sup>-10<sup>6</sup> M<sup>-1</sup> range, with <b>3d</b> showing the strongest affinity (<i>K<sub>b</sub></i> = 1.13 × 10<sup>6</sup> M<sup>-1</sup>), consistent with an intercalative binding mode. Docking studies with human DNA (PDB ID: 1G3X) revealed stabilizing hydrogen bonds, π-π stacking, and hydrophobic contacts that corroborated the experimental findings. Electronic properties were further explored through density functional theory calculations at the B3LYP level, which demonstrated that frontier orbital parameters-particularly highest occupied molecular orbital-lowest unoccupied molecular orbital gaps and electrophilicity indices-correlated well with DNA-binding behavior, offering mechanistic insight into the electronic contributions to molecular recognition. <i>In silico</i> Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling suggested favorable pharmacokinetic attributes and drug-like properties. All derivatives promoted UV-induced cleavage of supercoiled pBR322 DNA, underscoring their potential as photoactive nuclease mimetics. These results identify benzoxazole-isoxazole hybrids as promising scaffolds for DNA-targeted applications in medicinal chemistry and chemical biology.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-33"},"PeriodicalIF":1.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenshuang Zou, Kashif Bashir, Rafia Batool, Maria Nasim, Hafiza Fakhira Ameer, Maryam Ali
{"title":"Molecular analysis of genes <i>MICA</i>, <i>GPC3, PNPLA3,</i> and <i>TM6SF2</i> polymorphisms in patients of hepatocellular carcinoma.","authors":"Wenshuang Zou, Kashif Bashir, Rafia Batool, Maria Nasim, Hafiza Fakhira Ameer, Maryam Ali","doi":"10.1080/15257770.2026.2705881","DOIUrl":"https://doi.org/10.1080/15257770.2026.2705881","url":null,"abstract":"<p><p>Associations of the <i>MICA</i> (rs2596542), <i>GPC3</i> (rs2267531), <i>PNPLA3</i> (rs738409), and <i>TM6SF2</i> (rs58542926) gene variants with the susceptibility to developing Hepatocellular Carcinoma (HCC) were studied. Blood samples from 600 subjects, including 300 HCC patients and 300 age- and gender-matched controls, were collected from different hospitals in Punjab, Pakistan. Genomic DNA was extracted from blood, and PCR was performed. The results showed that the mutant (TT) of the rs2596542 of the <i>MICA</i> gene is significantly associated with a decreased risk of HCC, while the heterozygote (CT) of the same polymorphism shows a significantly high association with increased HCC risk of 2-fold. In the case of the rs2267531 polymorphism of the <i>GPC3</i> gene, the mutant (GG) is significantly associated with decreased risk of HCC. In contrast, the heterozygous genotype (AG) of this polymorphism exhibited a highly significant association with a 7-fold higher risk of liver cancer. In the rs738409 variants of gene <i>PNPLA3</i>, heterozygous (AG) has a highly significant association with hepatocellular carcinoma, with increased risk of hepatocellular carcinoma by 2-fold. In rs58542926, a homozygous mutant (GG) also shows a substantial correlation with HCC, with increased risk of HCC up to 2-fold. In contrast, the heterozygous (AG) genotype of the rs58542926 SNP shows a highly significant relationship with decreased risk of HCC.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-20"},"PeriodicalIF":1.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic and prognosis of benign and malignant early pulmonary nodules using serum miR-500a-3p combined with CT signs.","authors":"Haiyan Chen, Yan Liu, Junjie Zhang","doi":"10.1080/15257770.2026.2697800","DOIUrl":"https://doi.org/10.1080/15257770.2026.2697800","url":null,"abstract":"<p><p>Accurate differentiation and risk assessment of pulmonary nodules are central to clinical management, but precise tools are still limited, and delays in distinguishing benign from malignant nodules can lead to unnecessary procedures or missed diagnoses, highlighting the urgent need for reliable biomarkers. This study included 114 patients with pathologically confirmed pulmonary nodules, from whom baseline clinical data, serum samples, and CT imaging were collected, and a diagnostic model integrating miR-500a-3p, nodule density, and diameter was established. In vitro, lung cancer cells were transfected with miR-500a-3p mimics to assess proliferation, migration, and invasion via CCK-8 and Transwell assays, and luciferase reporter assays were performed to validate the direct target of miR-500a-3p. Serum miR-500a-3p expression was lower in malignant nodules than in benign nodules, and a model incorporating miR-500a-3p, nodule density, and diameter demonstrated diagnostic accuracy (AUC = 0.887). High miR-500a-3p expression predicted longer progression-free survival, whereas low expression and large diameter were independent adverse prognostic factors, and the integrated model demonstrated concordance with pathological findings (Kappa = 0.636). In vitro, miR-500a-3p was markedly downregulated in lung cancer cell lines, and its overexpression significantly inhibited cell proliferation, migration, and invasion, while luciferase reporter assays confirmed that AFF4 is a direct target of miR-500a-3p. Serum miR-500a-3p aids in distinguishing malignant pulmonary nodules and predicting prognosis, and combining it with CT features enhances diagnostic accuracy; in vitro experiments confirmed that miR-500a-3p suppresses lung cancer cell proliferation, migration, and invasion and directly targets AFF4. Clinically, this model enables noninvasive risk stratification to guide -surgical decisions and follow-up planning, thereby improving -personalized patient management.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-17"},"PeriodicalIF":1.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Partial base pairing between 5' and 3' UTRs artificially regulates IVT mRNA expression levels.","authors":"Nao Hosoda, Atsushi Takasu, Kohei Nakanishi, Kentaro Hayashi, Shunsuke Saito, Naoyuki Yamada, Kenji Tsuge","doi":"10.1080/15257770.2026.2698790","DOIUrl":"https://doi.org/10.1080/15257770.2026.2698790","url":null,"abstract":"<p><p>Eukaryotic mature mRNAs possess a 5' cap and a 3' polyadenylate tail (poly(A)), both of which are essential for regulating mRNA expression levels. This regulation is structurally based on the circularization of mRNA, mediated by physical interactions among the 5' cap-binding protein eIF4E, the 3' poly(A)-binding protein PABPC1, and the translation initiation factor eIF4G, which bridges eIF4E and PABPC1. Here, we demonstrate that partial base pairing between the 5' and 3' untranslated regions (UTRs) of <i>in vitro-</i>transcribed (IVT) mRNAs promotes circularization and artificially boosts the expression levels. The expression levels of IVT mRNAs are influenced by the patterns formed by the lengths of the complementary and non-complementary regions between the UTRs. Moreover, we observed a sigmoidal relationship between the expression levels and Gibbs free energy changes resulting from 5'-3' UTR pairing. Collectively, these findings provide a novel framework for the rational design of 5' and 3' UTRs in IVT mRNAs and for predicting their expression levels based on thermodynamic parameters.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-18"},"PeriodicalIF":1.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}