IF 5 3区生物学

RNA Pub Date : 2026-04-16 DOI: 10.1261/rna.080749.125

Marko Jörg, Marco Kristen, Lukas Walz, Christine Lietz, Max Müller, Sebastian Nathal, Virginie Marchand, Yuri Motorin, Marie-Luise Winz, Mark Helm, Kristina Friedland

{"title":"Complementary DNA oligonucleotide direct in-gel quantification (cDINGQ) for precise tRNA fragment analysis.","authors":"Marko Jörg, Marco Kristen, Lukas Walz, Christine Lietz, Max Müller, Sebastian Nathal, Virginie Marchand, Yuri Motorin, Marie-Luise Winz, Mark Helm, Kristina Friedland","doi":"10.1261/rna.080749.125","DOIUrl":"10.1261/rna.080749.125","url":null,"abstract":"tRNA-derived fragments have emerged as critical regulators in various biological processes, but reliable methods for their quantification remain a challenge due to their small size and extensive RNA modifications. In this study, we present the newly developed Complementary DNA Oligonucleotide Direct In-Gel Quantification (cDINGQ) method for tRF analysis and compare it with traditional radioactive [32P] northern blotting, nonradioactive approaches, and high-throughput Illumina sequencing under different experimental conditions. The cDINGQ method, utilizing Cy5-labeled hybridization probes, offers high specificity and sensitivity for detecting tRFs with significantly reduced processing time and costs. By applying these techniques to an Alzheimer's disease (AD) cell model, we demonstrate the reliability of these methods in detecting subtle variations in tRF abundance. Our findings highlight the sensitivity, specificity, and applicability of each method, addressing limitations such as RNA input requirements and probe hybridization conditions. The study further explores the utility of these methods for detecting tRFs in various biological contexts, emphasizing their potential for future research and biomarker discovery in disease-related studies.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"736-756"},"PeriodicalIF":5.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087019","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

PTBP1 controls miRNA loading on target RNAs: lessons from the CyCoNP lncRNA. PTBP1控制靶rna上的miRNA装载：来自CyCoNP lncRNA的教训。

IF 5 3区生物学

RNA Pub Date : 2026-04-16 DOI: 10.1261/rna.080705.125

Alessandro Grazzi, Fabio Desideri, Irene Bozzoni

{"title":"PTBP1 controls miRNA loading on target RNAs: lessons from the CyCoNP lncRNA.","authors":"Alessandro Grazzi, Fabio Desideri, Irene Bozzoni","doi":"10.1261/rna.080705.125","DOIUrl":"10.1261/rna.080705.125","url":null,"abstract":"The concerted action of regulatory RNA and RNA binding proteins (RBPs) provides cells with highly versatile and transient tools to fine-tune gene expression in a broad variety of cellular systems (Unfried and Ulitsky, Nat Cell Biol 24: 608-615 [2022]; Hentze et al., Nat Rev Mol Cell Biol 19: 327-341 [2018]; Suzuki et al., Nat Genet 50: 657-661 [2018]). In this work, we explore the function of a specific interaction between PTBP1 and the cytoplasmic long noncoding RNA (lncRNA) CyCoNP, highly expressed in neural progenitors (Desideri et al., NAR 52: 9936-9952 [2024]), in which the RBP regulates the abundance of the lncRNA by a miRNA-mediated mechanism. PTBP1 is a well-known splicing regulator, although limited and peculiar examples of its involvement in other cellular processes, such as IRES-dependent translation and miRNA recognition of target RNAs, have been described (Dorn et al., Cell Death Dis 14: 6429 [2023]; Kim et al., Nat Commun 12: 5057 [2021]). We have recently characterized CyCoNP lncRNA as a regulator of NCAM1, which acts through a mechanism that involves direct RNA-RNA interaction with NCAM1 mRNA, balancing the availability and the localization of miR-4492 in its vicinity (Desideri et al., NAR 52: 9936-9952 [2024]). Here we expand the repertoire of molecular players acting in this circuitry by describing a direct interaction between PTBP1 and CyCoNP lncRNA. Through endogenous RNA purification, protein immunoprecipitation, and exploiting CyCoNP mutant constructs, we found that PTBP1, when interacting with CyCoNP, hampers miR-4492 binding to the lncRNA and in turn impedes its regulation on NCAM1 mRNA. This work aims to expand the biochemical characterization of regulatory networks relying on RBPs and their cognate target RNAs, highlighting the relevance of the analysis of the subcellular environment for each case of study.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"612-621"},"PeriodicalIF":5.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114063","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

Blocky proline/glutamine patterns in the SFPQ intrinsically disordered region dictate paraspeckle formation as a distinct membraneless organelle. 块状脯氨酸/谷氨酰胺模式在SFPQ内在无序区域指示副斑形成作为一个独特的无膜细胞器。

IF 5 3区生物学

RNA Pub Date : 2026-04-16 DOI: 10.1261/rna.080769.125

Hiro Takakuwa, Takao Yoda, Tomohiro Yamazaki, Tetsuro Hirose

{"title":"Blocky proline/glutamine patterns in the SFPQ intrinsically disordered region dictate paraspeckle formation as a distinct membraneless organelle.","authors":"Hiro Takakuwa, Takao Yoda, Tomohiro Yamazaki, Tetsuro Hirose","doi":"10.1261/rna.080769.125","DOIUrl":"10.1261/rna.080769.125","url":null,"abstract":"Membraneless organelles (MLOs) formed through phase separation play crucial roles in various cellular processes. Many MLOs remain spatially compartmentalized, avoiding fusion or engulfment. MLOs are formed by dynamic multivalent interactions, often mediated by proteins with intrinsically disordered regions (IDRs). However, the molecular principles behind how IDRs maintain MLO independence remain poorly understood. Here, we investigated the proline/glutamine (P/Q)-rich IDR of SFPQ, a protein identified as a key factor in segregating paraspeckles from nuclear speckles. Paraspeckle segregation analyses, using SFPQ mutants tethered to NEAT1_2 long noncoding RNA, revealed that P/Q residues within the SFPQ IDR, conserved from humans to zebrafish, are crucial for its segregation activity. Beyond amino acid composition, the blocky patterns of P/Q residues, in which proline- and glutamine-rich blocks are repetitively arranged, are required for segregation from nuclear speckles. Among human IDRs exhibiting PQ-block patterns, BRD4 IDR shows strong sequence similarity to the SFPQ IDR and exhibits comparable segregation activity. Molecular dynamics simulation suggests that the PQ-blocky patterns required for the paraspeckle segregation do not correlate with the IDR characteristics necessary for self-assembly. Thus, these data suggest that the PQ-blocky patterns in IDRs represent a previously uncharacterized property that contributes to MLO independence, possibly through a mechanism distinct from the conventional phase separation-promoting function of IDRs.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"688-703"},"PeriodicalIF":5.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030579","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

Optimal stability of a highly conserved RNA G4 in PDCoV nsp8 supports viral proliferation. PDCoV nsp8中高度保守的RNA G4的最佳稳定性支持病毒增殖。

IF 5 3区生物学

RNA Pub Date : 2026-04-16 DOI: 10.1261/rna.080834.125

Puxian Fang, Congbao Xie, Ting Cheng, Jingjing Sui, Yan Cheng, Tong Ding, Jiahui Guo, Yuhan Zhang, Liurong Fang, Dengguo Wei, Shaobo Xiao

{"title":"Optimal stability of a highly conserved RNA G4 in PDCoV nsp8 supports viral proliferation.","authors":"Puxian Fang, Congbao Xie, Ting Cheng, Jingjing Sui, Yan Cheng, Tong Ding, Jiahui Guo, Yuhan Zhang, Liurong Fang, Dengguo Wei, Shaobo Xiao","doi":"10.1261/rna.080834.125","DOIUrl":"10.1261/rna.080834.125","url":null,"abstract":"Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, primarily causes diarrhea in piglets and has the potential for cross-species transmission to humans. The recent detection of PDCoV in Haitian children underscores the urgent need for developing antiviral therapeutic strategies. G-quadruplexes (G4s) are implicated in the modulation of viral infection; however, their identification and roles in the PDCoV life cycle remain unclear. Here, we identified a highly conserved G4 structure, designated PDCoV-G4, located within the coding region of PDCoV nonstructural protein 8 (nsp8). PDS and TMPyP4, two well-known G4-binding ligands, were found to target PDCoV-G4 and exhibit anti-PDCoV activity. Interestingly, PDS stabilizes the structure of PDCoV-G4, while TMPyP4 disrupts it. The recombinant PDCoV with G4-disruptive mutations (rPDCoV-nsp8mut) displays resistance to both PDS and TMPyP4. Utilizing an embryonated chicken egg (ECE) infection model, we observed that TMPyP4 provides superior protective effects for rPDCoV-wt-infected ECEs compared to PDS. However, both PDS and TMPyP4 exhibited diminished protective effects on chicken embryos infected with rPDCoV-nsp8mut, relative to rPDCoV-wt, further confirming their in vivo antiviral activity through targeting PDCoV-G4. These findings demonstrate that the PDCoV-G4 plays a crucial regulatory role in the PDCoV life cycle and pathogenicity, representing a potential target for antiviral therapy.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"672-687"},"PeriodicalIF":5.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053811","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

Structure-informed mutagenesis identifies combinatorial contributions to mouse insulin receptor IRES function. 结构信息突变确定了小鼠胰岛素受体IRES功能的组合贡献。

IF 5 3区生物学

RNA Pub Date : 2026-04-16 DOI: 10.1261/rna.080775.125

William B Dahl, Tammy C T Lan, Silvia Rouskin, Michael T Marr

{"title":"Structure-informed mutagenesis identifies combinatorial contributions to mouse insulin receptor IRES function.","authors":"William B Dahl, Tammy C T Lan, Silvia Rouskin, Michael T Marr","doi":"10.1261/rna.080775.125","DOIUrl":"10.1261/rna.080775.125","url":null,"abstract":"Cells under stress shift their proteome by repressing cap-dependent translation initiation. RNA elements called internal ribosome entry sites (IRES) can allow key cellular transcripts to remain efficiently translated to support an effective stress response. We previously determined that the 5' untranslated region (5'UTR) of the insulin receptor mRNA possesses a capacity for IRES activity that is conserved from insects to mammals. Well-characterized IRESs depend on RNA structures that reduce the protein requirements for translation initiation, thus circumventing translation inhibition. While there are several examples of viral IRES structures solved in vitro, the RNA secondary structures of cellular IRESs remain elusive, and little information exists about the secondary structures of these RNAs in vivo. Here we probe the secondary structure of the Insr 5'UTR IRES along with two well-studied viral IRESs from hepatitis C virus and encephalomyocarditis virus using dimethyl sulfate mutational profiling by sequencing (DMS-MaPseq) in vitro and in cells. We find that the structures of viral IRESs in a cellular environment are largely consistent with their known in vitro structures. Using DMS-MaPseq probing as a constraint, we generated a model of the RNA secondary structure of the mouse insulin receptor 5'UTR. With this model as a guide, we employed a mutation strategy which allowed us to identify a conserved segment of RNA, distal from the translation start codon, that is critical for Insr IRES function. This knowledge informed the design of a minimal IRES element with equivalent activity to the full-length Insr 5'UTR across translation contexts.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"654-671"},"PeriodicalIF":5.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053775","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

Uridine analogs prevent stress granule formation, not by blocking PKR recognition, but by inhibiting the synthesis of T7 RNA polymerase byproducts. 尿苷类似物阻止应激颗粒的形成，不是通过阻断PKR识别，而是通过抑制T7 RNA聚合酶副产物的合成。

IF 5 3区生物学

RNA Pub Date : 2026-04-16 DOI: 10.1261/rna.080481.125

Sean J Ihn, Emily Jiang, Nevraj S Kejiou, Yifan E Wang, Laura Farlam-Williams, Alexander F Palazzo, Hyun O Lee

{"title":"Uridine analogs prevent stress granule formation, not by blocking PKR recognition, but by inhibiting the synthesis of T7 RNA polymerase byproducts.","authors":"Sean J Ihn, Emily Jiang, Nevraj S Kejiou, Yifan E Wang, Laura Farlam-Williams, Alexander F Palazzo, Hyun O Lee","doi":"10.1261/rna.080481.125","DOIUrl":"10.1261/rna.080481.125","url":null,"abstract":"mRNA-based therapeutics are commonly produced through T7 RNA polymerase-mediated in vitro transcription. Introducing these exogenous RNAs into human cells activates an RNA sensor protein kinase R (PKR), which suppresses translation initiation and reduces their therapeutic effectiveness. Incorporating uridine analogs into these transcripts prevents PKR activation and translation shutdown, but the underlying mechanism remains unclear. Here, we demonstrate that treating T7 RNA polymerase-produced transcripts with RNase III, which selectively degrades double-stranded RNA (dsRNA), blocks PKR activation and downstream translation-inhibition events, including eIF2α phosphorylation and stress granule formation in human cells. Interestingly, dsRNAs generated with uridine analogs robustly induce eIF2α phosphorylation and stress granules to the same extent as dsRNA containing uridine. These findings indicate that uridine analogs do not prevent PKR from detecting dsRNA. Instead, we show that uridine analogs decrease the production of T7 RNA polymerase byproducts, including antisense RNA and dsRNA, which activate PKR and downstream stress responses. Finally, we demonstrate that higher amounts of exogenous RNA, lacking T7 RNA polymerase byproducts, can induce stress granules independently of PKR and phospho-eIF2α, but dependent on stress granule scaffold proteins G3BP1 and G3BP2. Together, our findings show that uridine analogs mitigate PKR signaling not by blocking mRNA-PKR interactions but by minimizing dsRNA byproducts from T7 polymerase transcription. Furthermore, stress granule formation in response to high levels of exogenous RNA can occur through a mechanism that does not depend on PKR but relies on G3BP1 and G3BP2. These insights clarify the role of uridine analogs in PKR activation and may inform future therapeutic RNA design.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"539-554"},"PeriodicalIF":5.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030524","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

Nuclear basket subunits Nup211 and Rsm1 influence RNA 3'-processing and transcription termination in fission yeast. 核篮亚基Nup211和Rsm1影响裂变酵母RNA 3'的加工和转录终止。

IF 5 3区生物学

RNA Pub Date : 2026-04-13 DOI: 10.1261/rna.081007.126

Lauren Bednor, Aleksei Innokentev, Ana M Sanchez, Angela Sem, Beate Schwer, Stewart Shuman

{"title":"Nuclear basket subunits Nup211 and Rsm1 influence RNA 3'-processing and transcription termination in fission yeast.","authors":"Lauren Bednor, Aleksei Innokentev, Ana M Sanchez, Angela Sem, Beate Schwer, Stewart Shuman","doi":"10.1261/rna.081007.126","DOIUrl":"https://doi.org/10.1261/rna.081007.126","url":null,"abstract":"The fission yeast phosphate acquisition (PHO) regulon is repressed under phosphate-replete conditions by upstream lncRNA-mediated transcriptional interference. Inositol-1-pyrophosphates control PHO gene expression via their action as agonists of precocious PHO lncRNA 3'-processing/termination. Inositol pyrophosphatase-inactivating asp1-STF mutations that increase inositol-1-pyrophosphates elicit derepression of the PHO genes and a severe growth defect in YES medium. Previous studies demonstrated suppression of inositol pyrophosphate toxicosis by loss-of-function and hypomorphic mutations in 11 of the 14 subunits of the fission yeast Cleavage and Polyadenylation Factor (CPF) complex. Here, we report the identification and characterization of mutations in the Nup211 and Rsm1 subunits of the nuclear basket of the nuclear pore complex that suppress inositol pyrophosphate toxicosis. We localize Nup211's activity in asp1-STF toxicosis to the C-terminal segment that forms a globular module appended to the dimeric Nup211 coiled-coil of the nuclear basket strut. A triple-alanine mutation of a conserved Nup211 1821RDD1823 peptide sufficed to suppress asp1-STF toxicosis. We find that: (i) induced overexpression of the Nup211 C-terminal segment is itself toxic to fission yeast, and that this toxicity was abolished by the RDD-AAA mutation; and (ii) Nup211 C-terminal truncation confers synthetic growth defects when combined with loss-of-function mutations in CPF subunits Ppn1, Swd22, and Ssu72. Our results implicate the Nup211 C-terminus as part of a protein-protein interface that abets 3'-processing/termination.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676337","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

Both neighboring codon adjacent nucleotides and codon optimality influence mRNA decay rates. 邻近密码子邻近核苷酸和密码子最优性都影响mRNA的衰变速率。

IF 5 3区生物学

RNA Pub Date : 2026-04-13 DOI: 10.1261/rna.080900.125

Reed S Sorenson, Leslie E Sieburth

{"title":"Both neighboring codon adjacent nucleotides and codon optimality influence mRNA decay rates.","authors":"Reed S Sorenson, Leslie E Sieburth","doi":"10.1261/rna.080900.125","DOIUrl":"10.1261/rna.080900.125","url":null,"abstract":"Codon optimality-mediated decay (COMD) is a major pathway that determines mRNA decay rates in eukaryotes. Conservation of this pathway in plants has not been demonstrated. To identify codons that might influence cotranslational mRNA decay rates, we compared codon usage bias in Arabidopsis seedling-expressed mRNAs with their mRNA half-lives (t1/2s). Finding differences in codon usage between transcripts with short and long t1/2s led to a model of mRNA decay rate based on codon frequencies. This codon-decay rate model explained 21% of decay rate variance in Arabidopsis and was predictive of decay rates of synonymously recoded genes. In the COMD pathway, NOT3, a component of the CCR4-NOT deadenylation complex, can detect slow ribosome decoding and trigger decay cotranslationally. Because the N-terminal sensor domain of NOT3 is retained in plant genomes, it's likely that plants, yeast and humans use the same mechanism. However, codon optimality in Arabidopsis was not reading-frame dependent, suggesting that additional sequence features also contributed to decay rates. These features were computationally identified as specific adjacent nucleotides of neighboring codons. The influence of adjacent codons appears to be a conserved feature of cotranslational decay, as published datasets from wheat (Triticum aestivum) and fission yeast (Schizosaccharomyces pombe) also showed neighboring codon adjacent nucleotides to impact RNA decay rates. These findings show that codon sequence can influence mRNA decay rates independently of charged tRNA concentrations and suggest a paradigm of selection among synonymous codons that are decoded through wobble base pairing.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676345","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

Neuronal Subtype-Specific Ribosomal Protein mRNA Expression. 神经元亚型特异性核糖体蛋白mRNA表达。

IF 5 3区生物学

RNA Pub Date : 2026-04-09 DOI: 10.1261/rna.080954.126

Joaquin Garat, Sofia Niño-Rivero, Patricia Lagos, Andres Di Paolo, Pablo Smircich, Jose Sotelo-Silveira

{"title":"Neuronal Subtype-Specific Ribosomal Protein mRNA Expression.","authors":"Joaquin Garat, Sofia Niño-Rivero, Patricia Lagos, Andres Di Paolo, Pablo Smircich, Jose Sotelo-Silveira","doi":"10.1261/rna.080954.126","DOIUrl":"https://doi.org/10.1261/rna.080954.126","url":null,"abstract":"Current understanding recognizes that ribosomal proteins (RPs) have regulatory roles beyond their canonical structural functions in translation, raising the question of how their expression is organized across cell types. Given the diversity of neuronal cell types, understanding RP gene expression at the neuronal subtype level is an important and previously inaccessible question. Here, leveraging advances in single-cell transcriptomics, we analyzed single-cell RNA-seq datasets from the mouse cerebral cortex and hippocampus to examine RP mRNA expression across neuronal subtypes. We observed distinct RP mRNA expression profiles between excitatory and inhibitory neurons and found that higher Rps27 transcript levels in inhibitory neurons corresponded to increased Rps27 protein abundance. Beyond excitatory-inhibitory differences, RP mRNA expression further segregated across well-defined neuronal subclasses, with 59 of 84 RP genes differentially expressed, including enrichment of Rpl21 in Lamp5 and Rps27 in Vip interneurons. These patterns were consistent across cortical regions and reproducible across two independent single-cell technologies (Smart-seq2 and 10x Genomics). Analysis of aging- and stress-associated datasets revealed stable RP expression signatures, with limited phenotype-linked changes. Together, we present a comprehensive atlas of ribosomal protein gene expression at neuronal subclass resolution, revealing robust subclass-specific transcriptional signatures suggesting an underestimated regulatory layer.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646351","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

Synthesis and RNA Transcription of Colored 4-Selenouridine Triphosphate with Atom Mutagenesis. 带原子诱变的有色4-硒尿嘧啶三磷酸合成及RNA转录。

IF 5 3区生物学

RNA Pub Date : 2026-04-06 DOI: 10.1261/rna.080814.125

Dan Liu, Huiyan Sun, Sibo Jiang, Jin Pei, Zhen Huang

{"title":"Synthesis and RNA Transcription of Colored 4-Selenouridine Triphosphate with Atom Mutagenesis.","authors":"Dan Liu, Huiyan Sun, Sibo Jiang, Jin Pei, Zhen Huang","doi":"10.1261/rna.080814.125","DOIUrl":"https://doi.org/10.1261/rna.080814.125","url":null,"abstract":"4-Selenouridine (4SeU) is one of the naturally-occurring modifications of tRNAs, possibly maintaining the three-dimensional structural stability of tRNA and playing a critical role in stress responses. By using the 4-Se-atomic probe, previously we have revealed more insights into the RNA non-canonical interactions and uridine participation in the diversified RNA functions and structures. To further explore the Se-atomic probe, herein we report the first synthesis of 4-selenouridine triphosphate (4SeUTP) and the enzymatic incorporation of 4SeUTP into RNAs. Interestingly, we found that 4SeUTP possessed unique properties, including the red-shifted base absorption (365 nm), colored base (yellow) and higher base acidity (pKa = 7.85) reduced by Se-atom. Further, 4SeUTP was recognized by T7 RNA polymerase as well as UTP counterpart, and its transcription of RNAs (such as 4SeU-hammerhead ribozyme RNA) was up to the native level. Furthermore, the transcribed 4SeU-hammerhead ribozyme had higher cleaving activity (approximately 1.8 folds) than the corresponding native ribozyme. In conclusion, 4SeUTP can be a fine substrate of RNA polymerase, and the 4SeU-RNAs can be enzymatically synthesized with better catalytic activity, opening a new avenue for investigating the biochemical functions and structures of RNAs, especially catalytic RNAs.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627001","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

RNA最新文献