Ask about this productRelated genes to: XRN1 antibody
- Gene:
- XRN1 NIH gene
- Name:
- 5'-3' exoribonuclease 1
- Previous symbol:
- -
- Synonyms:
- SEP1
- Chromosome:
- 3q23
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-12
- Date modifiied:
- 2014-11-18
Related products to: XRN1 antibody
Related articles to: XRN1 antibody
- Innate immune activation is a major driver of unmodified in vitro-transcribed (IVT) mRNA degradation; however, how modified IVT mRNAs are degraded, and the related regulation mechanisms, remain poorly understood. Through a focused screen of viral- and host-derived immune suppressors, we identify 13 factors that enhance mRNA performance, with SOCS1 and the coronaviral membrane protein (M) emerging as the most potent. Multi-omics analyses reveal that pseudouridine-modified IVT mRNA undergoes rapid deadenylation and predominant 3'-5' decay, followed by bidirectional degradation, closely resembling endogenous mRNA decay kinetics, and is extensively associated with canonical mRNA decay machineries. Mechanistically, IVT mRNA activates IFN-β signaling, which promotes processing body (P-body) formation and XRN1-mediated 5'-3' degradation. Suppression of IFN signaling by SOCS1 or M markedly enhances mRNA expression across diverse cell types, organoid systems, and murine disease models. Together, these findings define a type I interferon-P-body-XRN1 axis that constrains modified IVT mRNA stability and provides a framework for enhancing mRNA therapeutics. - Source: PubMed
Publication date: 2026/04/17
Zhang TinghongPeng XingQin JinlingZhu BinqiangZhang ShuaihuaDeng ShijieSong ZhiminHan YulongZheng HuiChen JingjingZhang YunWang YaofengZhang JingyuanZhou YuminRan PixinShao NingyiZhu BinChan YunshenMeng Shu - The accumulation of subgenomic flavivirus RNAs (sfRNAs) modulates viral fitness and pathogenicity in culture and . These noncoding RNAs are produced by incomplete digestion of the flavivirus genome by the cellular 5'-3' exoribonuclease (XRN1). Diverse flaviviruses have conserved RNA structural elements (RSEs) that map to their 3'-untranslated region (3'-UTR): Xrn-resistant RNA structures, dumbbell structures, and a 3'-stem loop (3'SL). Despite the importance of the 3'-UTR RSEs for flavivirus replication, the structural dynamics of sfRNA during flavivirus infection are understudied. Here, we use digital droplet PCR to quantify sfRNA levels during infection for a panel of mosquito-borne flaviviruses (MbFV) including dengue virus serotypes 1 (DENV1), 2 (DENV2), and 4 (DENV4), and Zika virus (ZIKV). We then used SHAPE-MaP on XRN1-digested, -transcribed sfRNAs from each virus to determine their secondary structures compared to the corresponding sfRNAs obtained from flavivirus-infected A549 cells. Results seen in-cell and were largely similar; however, motifs within the dumbbell, the small hairpin (sHP) directly upstream of the 3'-SL, and 3'-SL regions showed significant differences in the extent of nucleotide reactivity. These differences were consistent among the four flaviviruses examined and may indicate regions of sfRNA that are shielded by interaction with proteins or other nucleic acids during infection. However, strong protection indicative of sustained interaction was not apparent. Our findings suggest that sfRNA interactions with viral and host factors within the cell are few, occur via base-paired regions, or are highly transient. - Source: PubMed
Publication date: 2026/04/08
Bair Camden RVanInsberghe DavidLowen Anice CConn Graeme LNeufeldt Christopher J - Xrn1 is a highly conserved 5'→3' exoribonuclease that plays a central role in RNA turnover and quality control in eukaryotic cells. Although Xrn1 is known to degrade single-stranded RNA in a processive manner, the mechanism by which it engages and unwinds structured RNA remains incompletely understood. Here, we identify two evolutionarily conserved arginine residues, R100 and R101, located proximal to the active site, as critical determinants of duplex unwinding. Charge-conserving substitutions of these residues with lysine (R100K and R101K) markedly impair Xrn1's exonuclease activity, with R101K exhibiting a more severe functional defect. These effects are particularly pronounced on structured substrates, including RNA-DNA hybrids, implicating the local electrostatic environment in facilitating duplex destabilization via tight gripping 5' overhangs. Single-molecule Förster resonance energy transfer measurements reveal that Xrn1 unwinds duplexes in discrete steps, each corresponding to the melting of ~8-9 base pairs. Together, these findings uncover a charge-dependent mechanism of RNA duplex unwinding and establish distinct roles for conserved active site residues in modulating Xrn1's processivity on structured substrates. - Source: PubMed
Rhee JunhyukCho HyeokjinHong SemiYoo JungminJin Mi SunJin Suk-WonChang Jeong HoTong LiangLee Gwangrog - Arthropod-borne flaviviruses produce subgenomic RNAs (sfRNAs) from the highly conserved 3'-untranslated region (UTR). While most flaviviruses generate sfRNAs by resisting degradation from the host exoribonuclease XRN1, Japanese encephalitis virus (JEV) maintains sfRNA production even when XRN1 is depleted, suggesting an alternative mechanism. Using an in vitro RNA-dependent RNA polymerase (RdRp) assay, we identified a promoter-like element on the antigenome, designated (-)sfP, which exhibits transcriptional activity comparable to the well-characterized 5' stem-loop A (5'-SLA) promoter of the viral genome. In contrast, the complementary strand of 5'-SLA, termed (-)SLA, located at the 3'-terminus of antigenome, displayed only weak promoter activity. Both (-)SLA and (-)sfP RNAs were found to interact with viral RdRp and a similar set of host proteins, suggesting potential roles in regulating RNA synthesis from the antigenomic template. Detection of minus-strand sfRNA by Northern blot supports the existence of replication intermediates generated through RdRp-mediated transcription rather than simple degradation products. Together, these findings reveal a previously unrecognized promoter-like activity on the JEV antigenome that may contribute to sfRNA formation and genome replication. - Source: PubMed
Publication date: 2026/01/27
Chen Yi-ShiuanFan Yi-HsinTien Chih-FengChou Shih-JieChang Ruey-Yi - Unlike mRNA surveillance, ncRNA quality control is less well understood. While mRNA maturation is monitored by guard proteins that allow nuclear export of correctly processed transcripts or retention and degradation of faulty RNAs, such surveillance system is unknown for ncRNAs. This study investigates the maturation process of the snRNA U6 in Saccharomyces cerevisiae, revealing that this RNAPIII transcript undergoes quality control by established guard proteins and the novel factor Lhp1 (human La), which ensures proper loading of the Lsm-ring in the nucleus. Subsequent Mex67 binding facilitates the nuclear export of pre-U6. In the cytoplasm, pre-U6 associates with Prp24 which assists in annealing with pre-U4. Defects in di-snRNP formation are identified by the guard proteins Npl3, Gbp2, and Hrb1. These proteins retain the RNA in the cytoplasm and recruit Dcp1 and Dcp2 for de-capping, along with Xrn1 for degradation of faulty pre-U6. Correctly assembled U4/U6 complexes are released from the guard proteins and imported back into the nucleus. This guard protein-mediated surveillance mechanism prevents faulty di-snRNPs to torpedo the spliceosome, underscoring the significance of the compartmented maturation and quality control of ncRNA. Additionally, the study illustrates that RNA surveillance mechanisms extend beyond coding RNAs and involve similar quality control mechanisms and proteins. - Source: PubMed
Wang XiaoxiaoGuo JianLi JingKrebber Heike