RNAPub Date : 2026-09-16DOI: 10.1261/rna.081081.126
Nozhat T Hassan, Anna E Sheppard, David L Adelson, Kathleen Collins
{"title":"Diversity and genome engineering applications of R2 non-LTR retrotransposons.","authors":"Nozhat T Hassan, Anna E Sheppard, David L Adelson, Kathleen Collins","doi":"10.1261/rna.081081.126","DOIUrl":"10.1261/rna.081081.126","url":null,"abstract":"<p><p>The R2 retrotransposon family has been a leading model system for studies of site-specific non-long-terminal-repeat retrotransposon mobility. More recently, avian R2 systems have been harnessed to implement stable sequence supplementation of the human genome. Investigations of R2 retrotransposons range from detailed biochemical studies of purified components to elucidation of the cellular processes that support new retrotransposon insertions. In addition, molecular and genetic studies have examined the persistence and diversification of R2 retrotransposons across animals. In publications starting from early 2024, an R2-encoded protein has been used in native form, or after modification, to insert transgene sequences of choice into heterologous genomes lacking an endogenous R2. Many of these genome engineering studies were launched using a historically accumulated reporting of R2 sequences informative for understanding retrotransposon evolution but not intended as a catalog of active R2 retrotransposons. Other groups approached R2 sequence identification by using or building consensus retrotransposon sequences from mostly short-read genome sequencing or genome assemblies. Here, we describe R2 sequence discovery, phylogeny, and annotation, and we consider their influence on R2 protein applications including gene addition to the human genome.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1560-1570"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631416","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.081170.126
Wayne O Hemphill, Arthur J Zaug, Cody J S Hecht, Thomas R Cech
{"title":"Human vault RNAs exhibit diverse expression patterns and interlocus compensation.","authors":"Wayne O Hemphill, Arthur J Zaug, Cody J S Hecht, Thomas R Cech","doi":"10.1261/rna.081170.126","DOIUrl":"10.1261/rna.081170.126","url":null,"abstract":"<p><p>In 1986, a class of small, noncoding RNAs was discovered in association with an enormous, enigmatic ribonucleoprotein complex-the \"vault\" particle-and thus dubbed vault RNAs (vtRNAs). However, it has since been recognized that the vast majority (≥95%) of these noncoding vtRNA molecules are not associated with the mysterious vaults, raising questions about their potential independent function(s). Moreover, humans express four vtRNAs from two different loci, and debate has arisen about whether the vtRNA paralogs share any functional connection, and whether they should remain classified together. Herein, we report the expression patterns of the four <i>VTRNA</i> paralogs in a variety of human cell lines, including various single- and multigene <i>VTRNA</i>-knockout cell lines. Knockout of one or more of the three <i>VTRNA1</i> genes leads to increased expression of vtRNA2-1, suggesting that their biological functions are related. Additionally, we interrogated the effects of vtRNA knockout on HEK293T cell growth, viability, and viral infection, and were unable to replicate previously reported associations. Collectively, our findings point to a potential functional connection between even the most distantly related human vtRNA paralogs, while reaffirming that their biological roles and mechanisms still require critical study.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1643-1662"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631538","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.081235.126
Apurba Sarkar, Shreya Ghosh, Beate Schwer, Stewart Shuman
{"title":"Trypanosome Tpt1 is a bifunctional enzyme composed of tandem DEDDh nuclease and RNA 2'-phosphotransferase domains.","authors":"Apurba Sarkar, Shreya Ghosh, Beate Schwer, Stewart Shuman","doi":"10.1261/rna.081235.126","DOIUrl":"https://doi.org/10.1261/rna.081235.126","url":null,"abstract":"<p><p>RNA 2'-phosphotransferase Tpt1 is a widely distributed enzyme that removes an internal RNA 2'-phosphate by transfer to NAD+. Tpt1 is essential in fungi, where it erases the 2'-PO4 mark installed by tRNA ligase during tRNA splicing. Tpt1 enzymes from bacteria, archaea, fungi, and metazoa are monofunctional units composed of RNA-binding and NAD+-binding lobes. The lone exception to date is fission yeast Tpt1, which consists of an N-terminal RNA 2'-phosphotransferase catalytic domain fused to a C-terminal domain homologous to budding yeast iron-sulfur cluster assembly factor Yae1. Here we report that the Tpt1 homologs of kinetoplastid protozoa are bifunctional enzymes composed of an N-terminal DEDDh-type nuclease domain linked to a C-terminal 2'-phosphotransferase domain. Characterization of Trypanosoma brucei Tpt1 (TbrTpt1) revealed that: (i) the C-terminal domain TbrTpt1-(298-540) is an autonomous module that catalyzes 2'-PO4 transfer to NAD+ via an RNA-2'-phospho-(ADP-ribose) intermediate; (ii) TbrTpt1-(299-540) is active in tRNA splicing in vivo when expressed in budding yeast tpt1∆ cells; and (iii) TbrTpt1 is a manganese-dependent 3'-exonuclease adept at resecting DNA and RNA single strands. TbrTpt1's RNA exonuclease is blocked by a 2' terminal phosphate. TbrTpt1 and TbrTpt1-(298-540) can remove a 2'-terminal phosphate via transfer to NAD+, albeit much less efficiently than removal of an internal 2'-phosphate.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983531","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.081174.126
Sven Willen, Despoina Myti, Razan Obeidat, Francisco Casado, Solmaz Khaghani Raziabad, Claudio Nardiello, Stefan Günther, Per Haberkant, Frank Stein, Muzamil Majid Khan, Rainer Pepperkok, Verena Rickert-Zacharias, István Vadász, Susanne Herold, Anne Hilgendorff, Ivana Mižik, Werner Seeger, Rory E Morty
{"title":"Functional delivery of commercially available microRNA mimics to the organs of developing mice.","authors":"Sven Willen, Despoina Myti, Razan Obeidat, Francisco Casado, Solmaz Khaghani Raziabad, Claudio Nardiello, Stefan Günther, Per Haberkant, Frank Stein, Muzamil Majid Khan, Rainer Pepperkok, Verena Rickert-Zacharias, István Vadász, Susanne Herold, Anne Hilgendorff, Ivana Mižik, Werner Seeger, Rory E Morty","doi":"10.1261/rna.081174.126","DOIUrl":"10.1261/rna.081174.126","url":null,"abstract":"<p><p>MicroRNAs are pivotal regulators of organ and tissue homeostasis and development, and pathogenic mediators of disease. While antagonism of specific microRNA species in vivo is easily accomplished in experimental animal models using locked nucleic acid (LNA)-stabilized antimiRs, microRNA mimicry-that is, increasing the abundance of specific microRNA species-in experimental animals is more challenging. In this study, commercially available naked LNA-stabilized oligonucleotides designed as microRNA mimics were assessed for efficacy in newborn mouse pups, which frequently serve as models for normal human development, or neonatal and pediatric disease. Mimics targeting miR-497a-5p commercially marketed for in vitro or in vivo use were examined for distribution to five organs in developing mouse pups after parenteral administration. Mimics were most effectively delivered to the liver, and in limited instances also to the heart and kidneys, but could not be detected in the brain or lungs. A combination of bulk RNA-seq transcriptomic screening and proteomic screening of liver homogenates revealed that mimics delivered to the liver were functional, either reducing the abundance of the <i>Tff3</i> mRNA transcript, or the abundance of N4bp1 or Mt2 proteins, all of which are cognate targets of miR-497a-5p. Furthermore, the data presented here demonstrate that LNA-stabilized mimics for miR-497a-5p were short-lived in vivo, yet impacted the abundance of both primary and secondary targets of miR-497a-5p albeit with demonstrable hepatotoxicity. This study concludes that while microRNA mimicry using commercially available naked LNA-stabilized oligonucleotides is possible, there remains tremendous scope-and need-for refinement of this technology.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1571-1589"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585094","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}
{"title":"Histidine 62 in ArfB is required for stop codon-independent peptidyl-tRNA hydrolysis on the stalled ribosome.","authors":"Daisuke Kurita, Kotone Furusawa, Takumi Kasuya, Hideka Tonosaki, Nobukazu Nameki, Hyouta Himeno","doi":"10.1261/rna.080874.125","DOIUrl":"10.1261/rna.080874.125","url":null,"abstract":"<p><p>Translating ribosomes can stall on mRNA for various reasons, including nuclease cleavage, arrest peptide sequences or ribosome collisions. In <i>Escherichia coli</i>, several ribosome rescue factors act to release ribosomes stalled at the 3' end of mRNA. Among these factors, ArfB can rescue stalled ribosomes without the help of other factors. ArfB consists of an N-terminal domain containing the catalytic GGQ motif, which mediates peptidyl-tRNA hydrolysis, and a C-terminal extension that functions as a sensor for recognizing stalled ribosomes. However, how these two regions coordinate to resolve ribosome stalling remains unclear. Here, using a reconstituted translation system, we found the functional importance of histidine residues in the N-terminal domain of ArfB. In particular, histidine at position 62 in <i>E. coli</i> ArfB was required for stop codon-independent fMet-tRNA hydrolysis, whereas its substitution did not affect affinity for the ribosome. Furthermore, directed hydroxyl radical probing revealed that H62A mutation did not significantly alter the overall positioning of either the N-terminal domain or the C-terminal extension of ArfB on the ribosome. These findings suggest that H62 contributes to ArfB function during a step following initial ribosome binding, thereby facilitating peptidyl-tRNA hydrolysis.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1663-1671"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631475","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.080852.125
Thomas G Brooks, Nicholas F Lahens, Antonijo Mrčela, Jianing Yang, Souparna Purohit, Amruta Naik, Emanuela Ricciotti, Shaon Sengupta, Peter S Choi, Gregory R Grant
{"title":"A systematic evaluation of the sources of nonuniform coverage in RNA-seq and limitations of current practices.","authors":"Thomas G Brooks, Nicholas F Lahens, Antonijo Mrčela, Jianing Yang, Souparna Purohit, Amruta Naik, Emanuela Ricciotti, Shaon Sengupta, Peter S Choi, Gregory R Grant","doi":"10.1261/rna.080852.125","DOIUrl":"10.1261/rna.080852.125","url":null,"abstract":"<p><p>RNA splicing is the focus of a vast array of studies in biology, as it is involved in many normal cellular functions and related abnormalities. RNA-seq remains the standard quantitative assay to interrogate splicing. The primary technical artifact of RNA-seq library prep is the nonuniformity in coverage across transcripts. This undermines the accuracy of isoform-level quantification. This nonuniformity is present in both bulk and single-cell RNA-seq and is purely artifactual as it is observed even when the sample contains only full-length transcripts. Therefore, understanding the source of this nonuniformity is of high importance. Here, we clarify the state of current knowledge and investigate the possible contributing factors. We demonstrate that no single factor can explain the phenomenon. Several approaches have previously been reported to improve uniformity, including reducing PCR ramp rates or cycle numbers, avoiding ribosomal depletion, using shorter fragment lengths, and using thermostable reverse transcriptases. We investigate all of these and demonstrate that none of them produce substantial improvements. We further investigate the possible sources of nonuniformity by assessing existing data sets with varying sample quality, PCR cycle number, reverse transcriptase, and technical or biological replicates. In addition, we generated novel data sets by varying PCR ramp rate, fragment length, and ribosomal depletion method. We demonstrate a connection of coverage with PCR that depends more on molecular abundance than PCR cycle number.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1612-1625"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621479","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.081112.126
Shin Ando, Jiro Kondo
{"title":"4MRNA: a new approach for nucleic acid molecular replacement using models with diverse parameter patterns.","authors":"Shin Ando, Jiro Kondo","doi":"10.1261/rna.081112.126","DOIUrl":"10.1261/rna.081112.126","url":null,"abstract":"<p><p>Structural analysis of nucleic acids lags behind that of proteins, partly because most fundamental structural analysis techniques have been primarily developed for proteins. The molecular replacement (MR) method, commonly used for phase determination in protein crystallography, encounters unique challenges when applied to nucleic acids. Nucleic acids can have different three-dimensional structures even with the same sequence, which often render database entries or predicted models unsuitable as search models for MR. To overcome the limitation, we developed a novel strategy termed 4MRNA, which stands for Massive Multi-type Model Molecular Replacement for Nucleic Acids. This method introduces a new principle for MR, which is the systematic creation of diverse search models through parameter adjustment. By identifying the parameters that critically influence MR and generating models based on their statistical analysis, 4MRNA can provide search models that closely approximate target structures and thereby improve the success rate of MR. Its effectiveness was validated across comprehensive test cases including canonical duplexes, duplexes with bulges and internal loops, the more complex structure of transfer RNA, and a previously unreported DNA structure. 4MRNA is anticipated to become an indispensable tool for nucleic acid structure determination, profoundly advancing fundamental research and extending its impact to wide-ranging applications including structure-based drug design and nucleic acid nanotechnology.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1544-1559"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472599","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.080985.126
Shibashis Paul, Sha Sun, Karmella Haynes, Tian Hong
{"title":"A continuum-based reaction-diffusion model for spread of gene silencing in chromosomal inactivation.","authors":"Shibashis Paul, Sha Sun, Karmella Haynes, Tian Hong","doi":"10.1261/rna.080985.126","DOIUrl":"10.1261/rna.080985.126","url":null,"abstract":"<p><p>Regulation of gene silencing in large chromosomal regions is crucial for development and disease progression. One example of massive gene silencing is X chromosome inactivation (XCI), a process essential for gene dosage compensation. During XCI, most genes in the chromosome are inactivated following the transcription of long noncoding RNA XIST. Recent experiments showed that the spread of silencing is restricted in space but the mechanism of controlling the spread remains unclear. Here, we develop a continuum-based, reaction-diffusion model that elucidates chromosomal inactivation through a regulatory network for XIST-mediated gene silencing. We find that the spread of XIST can be tuned by known negative feedback loops regulating its synthesis and degradation, and that the spread of gene silencing is controlled by a wave-pinning mechanism driven by global regulation of silencing complex together with local epigenetic regulators. We use a 3D chromosome structure inferred from experimental data and our modeling framework to show the spatiotemporal regulation for spread of gene silencing. Our method enables the investigation of the inactivation dynamics of large regions of chromosomes with varying degrees of the spread of gene silencing. Our model provides mechanistic insights that quantitatively relate gene regulatory networks to the tunability and stability of chromosomal inactivation.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":"32 10","pages":"1531-1543"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983600","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}
{"title":"AUA codon decoding by preferential use of tRNA<sup>Ile</sup>(UAU) in <i>Lactobacillus casei</i>.","authors":"Chie Tomikawa, Satoshi Okura, Gakuto Uesugi, Kodai Toda, Kazuyuki Takai","doi":"10.1261/rna.081092.126","DOIUrl":"10.1261/rna.081092.126","url":null,"abstract":"<p><p>Modified nucleosides at the first (wobble) position of tRNA anticodons play critical roles in accurate decoding of the genetic code. In bacteria, the isoleucine AUA codon is typically decoded by tRNA<sup>Ile</sup>(LAU), in which lysidine (L) at the wobble position of tRNA<sup>Ile</sup> with a CAU anticodon ensures discrimination from the methionine AUG codon. However, some bacteria, such as <i>Mycoplasma mobile</i>, lack tRNA<sup>Ile</sup>(LAU) and instead utilize tRNA<sup>Ile</sup>(UAU). In this organism, the unmodified uridine at the wobble position is thought to enable specific decoding of AUA while avoiding AUG recognition. In our previous study, we identified a lactic acid bacterium in which both tRNA<sup>Ile</sup>(LAU) and tRNA<sup>Ile</sup>(UAU) coexist. Here, we show that tRNA<sup>Ile</sup>(LAU) is scarcely aminoacylated in vivo, whereas tRNA<sup>Ile</sup>(UAU) is efficiently aminoacylated. Notably, the presence of 4-thiouridine (s<sup>4</sup>U) at position 8 inhibits IleRS-dependent aminoacylation of tRNA<sup>Ile</sup>(UAU) in vitro, suggesting a regulatory role of tRNA modification in this process. Moreover, tRNA<sup>Ile</sup>(LAU) exhibits incomplete discrimination between AUA and AUG codons and binds to AUG in the ribosomal A-site binding assays. In contrast, tRNA<sup>Ile</sup>(UAU) containing <i>N</i> <sup>6</sup>-threonylcarbamoyladenosine (t<sup>6</sup>A) at position 37 showed a tendency toward improved discrimination between AUA and AUG codons and preferentially recognized AUA at the ribosomal A site. These results indicate that AUA decoding is predominantly mediated by preferential use of tRNA<sup>Ile</sup>(UAU) rather than canonical tRNA<sup>Ile</sup>(LAU), revealing an alternative mechanism of codon decoding based on differential utilization of tRNA isoacceptors, and providing an additional layer of translational control in bacteria.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1590-1602"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412701","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}
RNAPub Date : 2026-09-16DOI: 10.1261/rna.081020.126
Marcus A Price, Maryia Trubitsyna, Jane E Paget, Benjamin W Baker, Frances Turner, Susan J Rosser
{"title":"Efficient production of a self-amplifying RNA vaccine sequence with the single subunit RNA polymerase from <i>Klebsiella</i> phage 32 utilizing the native AU initiating dinucleotide.","authors":"Marcus A Price, Maryia Trubitsyna, Jane E Paget, Benjamin W Baker, Frances Turner, Susan J Rosser","doi":"10.1261/rna.081020.126","DOIUrl":"10.1261/rna.081020.126","url":null,"abstract":"<p><p>RNA polymerase (RNAP) is the enzyme that produces RNA for an increasingly large variety of uses. The need for efficient industrial production of high quantities of mRNA was exemplified during the SARS-CoV-2 pandemic. While the RNAP from the T7 bacteriophage has been the gold standard for some time, it has certain limitations impeding efficient manufacturing of all RNA types, including production of long transcript self-amplifying RNA (saRNA). Here we present an alternative to T7 RNAP, identified from the <i>Klebsiella</i> bacteriophage 32 (KP32). We show KP32 RNAP to efficiently produce RNA of varying lengths, with a wide temperature, pH and salt tolerance range. We show KP32 RNAP to be capable of efficient production of an 11,551 nt self-amplifying RNA with its critical native initiating dinucleotide, AU. This represented a 9.3-fold improvement in production levels, relative to T7 RNAP.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1626-1642"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649094","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}