IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.080904.125

Daniel F Moakley, Ye Wang, Chaolin Zhang

{"title":"Onconeural antigen NOVA1 dysregulates RNA alternative splicing in breast cancer.","authors":"Daniel F Moakley, Ye Wang, Chaolin Zhang","doi":"10.1261/rna.080904.125","DOIUrl":"10.1261/rna.080904.125","url":null,"abstract":"The neuron-specific splicing factor NOVA1 was first discovered as an onconeural antigen ectopically expressed in breast tumors, causing rare autoimmune reactions and paraneoplastic neurological disorders (PNDs). The PND model suggests a plausible role of the tumor antigen expression in tumor suppression, whereas it has emerged that NOVA exhibits oncogenic activity in cell-based models. Whether NOVA mediates alternative splicing (AS) in native cancer remains unknown. Here we examine the AS profiles of breast invasive carcinoma (BRCA) tumor samples and demonstrate that aberrant NOVA1 overexpression led to the activation of neuron-like splicing patterns in many genes, including alternative exons targeted by NOVA in the brain. The splicing dysregulation is especially prevalent in cell periphery and cytoskeleton genes related to cell-cell communication, actin-based movement, and neuronal functions. We find that NOVA1-mediated AS is most prominent in Luminal A tumors and high NOVA1 expression in this subtype is associated with poorer prognosis. Our results suggest that ectopic NOVA1 in tumors has regulatory activity affecting pathways with high relevance to tumor progression.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1225-1233"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reconfigured immunity in Adar heterozygous and Adar Mavs Eif2ak2 (PKR) triple mutant mice. Adar杂合和Adar Mavs Eif2ak2 （PKR）三重突变小鼠的免疫重组

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.081079.126

Pavla Linhartová, Jaclyn E Quin, Tomáš Loja, Janka Melicherová, Qiupei Du, Anna Cherian, Dragana Vukić, David Modrý, Marie Tomandlová, Barbora Červená, Helena Stříbrná, Ann-Kristin Östlund Farrants, Andrea Knight, Liam P Keegan, Mary A O'Connell

{"title":"Reconfigured immunity in Adar heterozygous and Adar Mavs Eif2ak2 (PKR) triple mutant mice.","authors":"Pavla Linhartová, Jaclyn E Quin, Tomáš Loja, Janka Melicherová, Qiupei Du, Anna Cherian, Dragana Vukić, David Modrý, Marie Tomandlová, Barbora Červená, Helena Stříbrná, Ann-Kristin Östlund Farrants, Andrea Knight, Liam P Keegan, Mary A O'Connell","doi":"10.1261/rna.081079.126","DOIUrl":"10.1261/rna.081079.126","url":null,"abstract":"Adenosine deaminase acting on RNA 1 (ADAR1) deaminates adenosine to inosine in dsRNA. ADAR1 RNA editing marks cellular dsRNA as self, preventing aberrant activation of the antiviral dsRNA sensor MDA5. Adar Ifih1 (MDA5) or Adar Mavs double mutant pups escape Adar mutant aberrant interferon induction but die early. Here, we show that long-lived Adar Mavs Eif2ak2 (PKR) mice display a new residual defect: failure to maintain blood CD8+ T cells due to loss of an editing-independent function of ADAR1. Further dsRNA sensor-stripping in Adar Mavs Eif2ak2 Zbp1 mutants shows that loss of blood CD8+ T cells is not prevented. Challenging Adar +/- heterozygous or Adar Mavs Eif2ak2 mice with blood stage Plasmodium yoelii infection led to reduced parasitemia in Adar +/- mice by increased basal interferon. Unexpected reduced parasitemia in Adar Mavs Eif2ak2 mice is also likely due to interferon-related defects specific to hematopoietic cells, leading to altered populations of γδ T cells and other immune cells. The defects observed in this partially dsRNA sensor-stripped mouse suggest that different antiviral dsRNA sensors normally complement each other.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1234-1256"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential human telomerase RNA knockdown by antisense oligonucleotides reveals the existence and potential function of a robust RNA domain. 不同的人端粒酶RNA被反义寡核苷酸敲低揭示了一个强大的RNA结构域的存在和潜在的功能。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.081025.126

Natalie Bao Ying Lim, Maya Jeitany, Peter Dröge, Kah Wai Lim, Anh Tuân Phan

{"title":"Differential human telomerase RNA knockdown by antisense oligonucleotides reveals the existence and potential function of a robust RNA domain.","authors":"Natalie Bao Ying Lim, Maya Jeitany, Peter Dröge, Kah Wai Lim, Anh Tuân Phan","doi":"10.1261/rna.081025.126","DOIUrl":"10.1261/rna.081025.126","url":null,"abstract":"Telomere length governs replicative capacity and cellular fate. In most cancers, telomeres are maintained by telomerase, a holoenzyme comprising an RNA component (hTR), a protein component (hTERT), and associated accessory proteins. hTR contains two major domains with distinct primary interactions: a 5' domain that associates with hTERT, and a 3' domain that binds core H/ACA proteins. Beyond telomere maintenance, hTR also exerts extra-telomeric roles. Here, we identified a potent antisense oligonucleotide (ASO) against hTR, which inhibited telomerase activity, leading to telomere shortening and cell growth impairment. Surprisingly, this ASO only mediated hTR degradation up to nucleotide 209, leaving the 3' domain intact. Profiling of hTR using ASO tiling also supported this observation: whereas 3'-targeting ASOs could deplete the whole molecule, 5'-targeting ASOs could selectively deplete only the 5' domain, leaving the 3' domain intact, or even increase in abundance. Furthermore, the 3' domain persisted at a steady state following prolonged treatment and was detected in untreated cells, suggesting its natural existence and potential function.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1290-1306"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytosolic and ER-associated ribosomes share rRNA 2'-O-methylation landscapes across human cell types. 细胞质核糖体和er相关核糖体在人类细胞类型中共享rRNA 2'- o甲基化景观。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.081054.126

Ülkü Uzun, Anders H Lund

{"title":"Cytosolic and ER-associated ribosomes share rRNA 2'-O-methylation landscapes across human cell types.","authors":"Ülkü Uzun, Anders H Lund","doi":"10.1261/rna.081054.126","DOIUrl":"10.1261/rna.081054.126","url":null,"abstract":"Ribosome heterogeneity arising from variable rRNA 2'-O-methylation (2'-O-Me) has been proposed as a potential mechanism for translational specialization, but whether such heterogeneity contributes to compartment-specific translation remains unknown. Here, we systematically compare the 2'-O-Me landscapes of cytosolic and endoplasmic reticulum (ER)-associated ribosomes across three human cell types: HEK293 cells, H9-derived neural progenitor cells (NPCs), and neurons differentiated from these NPCs. Using detergent-based fractionation combined with RiboMeth-seq, we generate site-resolved rRNA methylation profiles for each compartment. Within each cell type, cytosolic and ER-associated ribosomes display highly similar 2'-O-Me patterns, with only modest compartment-specific differences observed at 18S:462 in NPCs and 28S:2043 in neurons. Across all samples, differences in 2'-O-Me patterns are more pronounced between cell types than between compartments. Together, these findings indicate that 2'-O-Me does not establish a broad ER-specific methylation signature, and is unlikely to be a major determinant of ribosome localization or function at the ER.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1265-1277"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

R3DCID: circular interaction diagrams for RNA and DNA 3D structures of all sizes. R3DCID: RNA/DNA的环形相互作用图。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.081031.126

Patrick Nyadjo Fonga, Syed Muhammed Abubaker, Joey Thaman, Craig L Zirbel

{"title":"R3DCID: circular interaction diagrams for RNA and DNA 3D structures of all sizes.","authors":"Patrick Nyadjo Fonga, Syed Muhammed Abubaker, Joey Thaman, Craig L Zirbel","doi":"10.1261/rna.081031.126","DOIUrl":"10.1261/rna.081031.126","url":null,"abstract":"There are over 21,000 atomic-resolution 3D structures containing RNA and/or DNA chains in the Protein Data Bank, ranging in size from 2 nt to tens of thousands. Most structures have more than one nucleic acid chain, and many have multiple models, assemblies, or symmetry operators. Nucleic acid 3D structures are formed by repetition of Watson-Crick base pairs and base stacking, but RNA (and increasingly DNA) is also shaped by non-Watson-Crick base pairs and various base-backbone interactions. It is difficult to comprehend the entirety of the interactions that form within and between chains in complex 3D structures; for example, there are several chains, over 5500 nt, and over 9700 pairwise interactions in one human ribosomal RNA 3D structure. Here we introduce R3DCID (RNA + DNA 3D structure Circular Interaction Diagram, pronounced \"red sid\"), a web service that produces circular arc representations of the pairwise interactions in all chains, models, assemblies, and symmetries in each nucleic acid structure in PDB. Diagrams have a uniform appearance and interpretation across all sizes and varieties of structures. Output is provided in PDF and SVG format for compact file sizes and smooth zooming and panning. R3DCID provides a new perspective on nucleic acid 3D structures; it serves as a guide to their overall structure and as a detailed map of the interactions that are critical to their function.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1213-1224"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-throughput experimental validation of novel hairpin ribozymes. 新型发夹核酶的高通量实验验证。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.081093.126

Kaitlyn Matteo, Eric J Hayden

{"title":"High-throughput experimental validation of novel hairpin ribozymes.","authors":"Kaitlyn Matteo, Eric J Hayden","doi":"10.1261/rna.081093.126","DOIUrl":"10.1261/rna.081093.126","url":null,"abstract":"The small self-cleaving hairpin ribozyme has served as a model for RNA structure and function and has been engineered for biotechnology applications. Hairpin ribozymes were thought to be rare with only four known examples, which limited the interpretation of their biological importance and the starting sequences for engineering efforts. Recently, a bioinformatics approach identified hundreds of different RNA sequences in metatranscriptomic data that matched a novel permutation of the hairpin ribozyme. However, the self-cleavage activity of most of these sequences has not been experimentally demonstrated. Here, a high-throughput sequencing-based approach was used to evaluate the cotranscriptional self-cleavage of 855 different hairpin ribozymes in parallel. The results showed that nearly all sequences can catalyze a self-cleavage reaction under these experimental conditions. In addition, we observed that rare nucleotides at highly conserved positions did not prevent observable ribozyme activity. The distribution of observed activity suggests that the metatranscriptomic sequences could contain random mutations from efficient wild-type ribozymes. The results further validate the bioinformatics approach that was used for ribozyme discovery and raise questions about the biological roles of these ribozymes in the diverse environments where they were discovered.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1257-1264"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated NMR/MD investigation reveals differences after reweighting in conformational ensembles of the GAAG and GCAA tetraloops. 综合NMR/MD研究揭示了GAAG和GCAA四环重加权后构象系的差异。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.081067.126

David Leopold, Andreas Oxenfarth, F Emil Thomasen, Felix Kümmerer, Robbin Schnieders, György Pinter, Anna Wacker, Hendrik R A Jonker, Boris Fürtig, Christian Richter, Kresten Lindorff-Larsen, Harald Schwalbe

{"title":"Integrated NMR/MD investigation reveals differences after reweighting in conformational ensembles of the GAAG and GCAA tetraloops.","authors":"David Leopold, Andreas Oxenfarth, F Emil Thomasen, Felix Kümmerer, Robbin Schnieders, György Pinter, Anna Wacker, Hendrik R A Jonker, Boris Fürtig, Christian Richter, Kresten Lindorff-Larsen, Harald Schwalbe","doi":"10.1261/rna.081067.126","DOIUrl":"10.1261/rna.081067.126","url":null,"abstract":"While the GNRA tetraloops are an extensively studied and common RNA motif, their dynamic NMR structures in solution integrating state-of-the-art NMR parameters such as residual dipolar couplings (RDC) and cross correlated relaxation rates (CCR) have previously not been determined. Given their dominant occurrence among tetraloops in the PDB and the advance of experimentally reweighted MD simulations, the present work aims at investigating the entire conformational space of two known tetraloop sequences by an extensive NMR investigation of NOEs, J-couplings constants, RDCs and CCRs. As classical structure calculation proved insufficient for the more dynamic tetraloop, we turned to Bayesian/maximum entropy reweighting of molecular simulations using our rich set of experiments. The resulting ensembles were clustered and compared to classically restrained structure calculations, structures from the PDB and models predicted by the prediction algorithms Farfar and AlphaFold 3. Our results show that GNRA-like tetraloops can vary in dynamic sampling of conformational space. They highlight the importance of individual experimental validation of computationally obtained dynamic ensembles and model predictions.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1199-1212"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reconstitution of antiviral Dicer activity in vitro reveals distinct contributions of RDE-4 dsRNA-binding motifs. 体外重建抗病毒Dicer活性揭示了RDE-4 dsrna结合基序的独特贡献。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.080917.125

Elaina P Boyle, P Joseph Aruscavage, Claudia D Consalvo, Brenda L Bass

{"title":"Reconstitution of antiviral Dicer activity in vitro reveals distinct contributions of RDE-4 dsRNA-binding motifs.","authors":"Elaina P Boyle, P Joseph Aruscavage, Claudia D Consalvo, Brenda L Bass","doi":"10.1261/rna.080917.125","DOIUrl":"10.1261/rna.080917.125","url":null,"abstract":"In Caenorhabditis elegans, antiviral RNA interference (RNAi) relies on the coordinated activity of Dicer (DCR-1), the helicase DRH-1, and the double-stranded RNA (dsRNA)-binding protein, RDE-4, yet the domain-specific contributions of RDE-4 remain unclear. Here, we reconstituted the antiviral complex from independently purified DCR-1•DRH-1 and RDE-4 to define how RDE-4 stabilizes and activates the complex. Addition of recombinant RDE-4 restored ATP hydrolysis and dsRNA cleavage to levels previously observed with the preassembled complex, and time course assays revealed that RDE-4 is essential for maintaining DCR-1•DRH-1 activity. Mutational analysis of RDE-4 revealed that both dsRBM2 and dsRBM3, but not dsRBM1, are required for reconstituting ATP hydrolysis and cleavage. Disruption of the KKxAK motif in dsRBM2 drastically reduced dsRNA affinity and abolished catalytic rescue despite preserving robust binding to DCR-1•DRH-1. Mass photometry and pulldown assays revealed that RDE-4 primarily forms DCR-1 containing complexes, predominantly through interaction with dsRBM3, with no evidence for stable interaction with DRH-1 alone. Functionally, RDE-4 enhanced DRH-1-driven ATP hydrolysis on both 52 and 106 bp dsRNAs, but cleavage efficiency showed strong length dependence, implicating dsRNA substrate length as an effector in this system. Our findings establish RDE-4 as an important stabilizer of the antiviral complex and reveal distinct roles for dsRBM2 and dsRBM3 in ATP hydrolysis and dsRNA cleavage. Furthermore, our results suggest that substrate length modulates RDE-4 function in the context of antiviral cleavage. These insights refine our understanding of antiviral RNAi in C. elegans and uncover regulatory mechanisms within the antiviral complex.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1328-1342"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of multiple paralogs of a small subunit ribosomal protein in Francisella tularensis. 土拉菌中一个小亚基核糖体蛋白的多个类似物的调控。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.080657.125

Sierra S Schmidt, Alexandra R Farah, Aisling Macaraeg, Daniel Floyd, Hannah S Trautmann, Kathryn M Ramsey

{"title":"Regulation of multiple paralogs of a small subunit ribosomal protein in Francisella tularensis.","authors":"Sierra S Schmidt, Alexandra R Farah, Aisling Macaraeg, Daniel Floyd, Hannah S Trautmann, Kathryn M Ramsey","doi":"10.1261/rna.080657.125","DOIUrl":"10.1261/rna.080657.125","url":null,"abstract":"Francisella tularensis is a highly infectious human pathogen that must replicate inside macrophage to cause disease. The ribosomes of F. tularensis can incorporate one of three different paralogs for the small ribosomal subunit protein bS21. One of these paralogs positively impacts translation of key virulence genes and promotes intramacrophage replication. Although ribosomal bS21 content influences F. tularensis virulence, the factors that control bS21 paralog production are not well understood. Here, we reveal that all three bS21 proteins influence the transcript abundance of the paralog important for virulence, bS21-2. In contrast, the other bS21 paralogs (bS21-1 and bS21-3) do not affect their own production. We further determined that the leader sequence of the bS21-2 mRNA is sufficient for bS21-mediated repression of mRNA abundance, suggesting that bS21-2 is autogenously regulated. Counterintuitively, we found that in cells lacking bS21-2, the increase in bS21-2-encoding mRNA does not lead to significant increases in protein production. This reduction in translation efficiency suggests that translation of the bS21-2 mRNA is controlled by other factors. Finally, we determined that bS21-2 exerts at least some of its effects on the bS21-2 transcript by decreasing its stability. Together, our findings suggest that F. tularensis may integrate multiple signals into a regulatory network to control the appropriate production of each bS21 paralog, and particularly the paralog important for virulence, bS21-2. This raises the possibility of a regulatory network that can both control ribosome composition in F. tularensis as well as virulence.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1278-1289"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CNOT10 is involved in the TTP-mediated AU-rich element-containing mRNA metabolism, independent of mRNA decay regulation. CNOT10参与ttp介导的富au元素mRNA代谢，独立于mRNA衰变调节。

IF 4.3 3区生物学

RNA Pub Date : 2026-07-16 DOI: 10.1261/rna.080942.126

Yukitomo Arao, Jason G Williams, Wi S Lai

{"title":"CNOT10 is involved in the TTP-mediated AU-rich element-containing mRNA metabolism, independent of mRNA decay regulation.","authors":"Yukitomo Arao, Jason G Williams, Wi S Lai","doi":"10.1261/rna.080942.126","DOIUrl":"10.1261/rna.080942.126","url":null,"abstract":"Tristetraprolin (TTP)/ZFP36 is an RNA binding protein that is involved in the turnover regulation of the target adenylate-uridylate-rich RNA element (ARE)-containing mRNAs. AREs are present in the 3'-untranslated region of transcripts expressed from many immediate-early genes, including cytokines and chemokines. It has been demonstrated that TTP-mediated posttranscriptional mRNA decay regulation is crucial for modulating physiological control, particularly in response to inflammatory stimulation. TTP is associated with the CCR4-NOT deadenylation complex through the TTP C-terminus to promote mRNA decay. However, it is not fully understood whether there are additional sites within TTP that contribute to its function through interacting with other factors. We analyzed the functionality of the unique tryptophan residues located in the TTP N-terminus using a cell-based assay system that consists of a tetracycline-responsive CMV promoter-driven, intron-inserted luciferase (LUC). This system enabled us to analyze TTP activity during both the early phase and the steady-state phase of gene expression, as well as in the posttranscriptional mRNA decay following the treatment of tetracycline analogs. Meanwhile, we identified putative TTP associates using a proximity labeling method. We found that tryptophan residues in the TTP N-terminus together with CNOT10, a component of the CCR4-NOT complex, were involved specifically in the reduction of the ARE-containing LUC mRNA level during the early phase of gene expression. However, they were not involved in the decay of LUC mRNA in the steady-state phase. We propose a novel posttranscriptional TTP functionality in the reduction of ARE-containing mRNA levels, which differs from the well-characterized mRNA decay activity.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1307-1319"},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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