RTCB

更新于：2025-05-07

基本信息

别名

3'-phosphate/5'-hydroxy nucleic acid ligase、C22orf28、FAAP

+ [4]

简介

Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity, and may function toward other RNAs.

关联

100 项与 RTCB 相关的临床结果

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100 项与 RTCB 相关的转化医学

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0 项与 RTCB 相关的专利（医药）

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174

项与 RTCB 相关的文献（医药）

2025-04-01·Journal of Biological Chemistry

Structural and biochemical characterization of the 3'-5' tRNA splicing ligases

Article

作者: Sroka, Małgorzata ; Czarnocki-Cieciura, Mariusz ; Jemielity, Jacek ; Śmietański, Mirosław ; Wycisk, Krzysztof ; Chamera, Sebastian ; Koziej, Łukasz ; Nowak, Jakub ; Chramiec-Głąbik, Andrzej ; Nowotny, Marcin ; Jaciuk, Marcin ; Warmiński, Marcin ; Gołębiowski, Filip ; Zajko, Weronika ; Glatt, Sebastian

In archaea and metazoa, tRNA exons are ligated by the RNA ligases RtcB and RTCB, respectively. The metazoan RTCB forms a stable complex with four additional subunits, DDX1, FAM98B, CGI99 and ASHWIN. The role and assembly of these four components remain elusive. Furthermore, we lack structural information of how RNA substrates are recognized by 3'-5' tRNA ligases. Here, we use thiol-based chemical cross-linking to confirm the involvement of specific residues of RtcB in RNA binding and we present a cryo-electron microscopy structure of the purified five-subunit D. rerio tRNA ligase complex. The structure implies that the DDX1 helicase module is mobile and can modulate the activity of RTCB. Taken together, the presented results enhance our mechanistic understanding of RNA binding by 3'-5' tRNA splicing ligases and architecture of the metazoan tRNA ligase complex.

2025-03-25·mSphere

Characterization of diet-linked amino acid pool influence on Fusobacterium spp. growth and metabolism

Article

作者: Allen-Vercoe, Emma ; Vancuren, Sarah J. ; Marcone, Massimo ; Robinson, Avery V.

ABSTRACT The genus Fusobacterium contains multiple proteolytic opportunistic pathogens that have been increasingly linked to colorectal cancer (CRC). “Oncomicrobes” such as these fusobacterial species within the gut microbiota may contribute to CRC onset and/or progression. Protein-rich diets may both directly increase CRC risk and enrich for proteolytic oncomicrobes, including Fusobacterium spp. Individual food substrates vary in amino acid content, and released amino acid content that is not absorbed in the small intestine may influence the growth of colonic proteolytic fermenters. Fusobacteria such as Fusobacterium spp. are known to preferentially metabolize certain amino acids. As such, some foods may better support the growth of these species within the colonic environment than others. To explore this, in this study, we created free amino acid pools (FAAPs) to represent proportions of amino acids in major proteins of three common dietary protein sources (soy, beef, and bovine milk). Growth curves were generated for 39 Fusobacterium spp. strains cultured in a dilute medium supplemented with each of the three FAAPs. Thereafter, amino acid use by 31 of the 39 Fusobacterium spp. strains in each FAAP treatment was assessed. FAAP supplementation increased growth metrics of all Fusobacterium spp. strains tested; however, the strains varied greatly in terms of the FAAP(s) generating the greatest increase in growth. Furthermore, the amino acid utilization strategy was highly variable between strains of Fusobacterium spp. Neither growth metrics nor amino acid utilization could be explained by species classification of Fusobacterium spp. strains. This report expands upon the previous knowledge of fusobacterial amino acid metabolism and indicates that proteolytic oncomicrobial activity should be assessed in the context of available protein sources. IMPORTANCEFusobacterium spp. including F. animalis , F. nucleatum , F. vincentii , and F. polymorphum are common oral commensals with emerging importance in diseases across multiple body sites, including CRC. CRC lesions associated with fusobacteria tend to result in poorer prognosis and increased disease recurrence. While Fusobacterium spp. are thought to colonize after tumorigenesis, little is known about the factors that facilitate this colonization. Protein-rich diets yielding readily metabolized free amino acids within the colon may promote the growth of proteolytic fermenters such as fusobacteria. Here, we show that variable concentrations of free amino acids within pools that represent different dietary protein sources differentially influence fusobacterial growth, including CRC-relevant strains of Fusobacterium spp. This work highlights the high degree of variation in fusobacterial amino acid utilization patterns and suggests differing proportions of dietary amino acids that reach the colon could influence fusobacterial growth.

2024-10-14·Nucleic Acids Research

RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer’s disease

Article

作者: Pérez-Navarro, Esther ; Guisado-Corcoll, Anna ; Torres, Adrian Gabriel ; Pérez-Sisqués, Leticia ; Canal, Mercè ; Garcia-Segura, Pol ; Malagelada, Cristina ; Molina-Porcel, Laura ; Campoy-Campos, Genís ; Santamaria, Enrique ; Fernández-Irigoyen, Joaquín ; Martí, Eulàlia ; Giralt, Albert ; de Pouplana, Lluís Ribas ; Chicote-González, Almudena ; Solana-Balaguer, Julia ; Alberch, Jordi

AbstractRTP801/REDD1 is a stress-responsive protein overexpressed in neurodegenerative diseases such as Alzheimer’s disease (AD) that contributes to cognitive deficits and neuroinflammation. Here, we found that RTP801 interacts with HSPC117, DDX1 and CGI-99, three members of the tRNA ligase complex (tRNA-LC), which ligates the excised exons of intron-containing tRNAs and the mRNA exons of the transcription factor XBP1 during the unfolded protein response (UPR). We also found that RTP801 modulates the mRNA ligase activity of the complex in vitro since RTP801 knockdown promoted XBP1 splicing and the expression of its transcriptional target, SEC24D. Conversely, RTP801 overexpression inhibited the splicing of XBP1. Similarly, in human AD postmortem hippocampal samples, where RTP801 is upregulated, we found that XBP1 splicing was dramatically decreased. In the 5xFAD mouse model of AD, silencing RTP801 expression in hippocampal neurons promoted Xbp1 splicing and prevented the accumulation of intron-containing pre-tRNAs. Finally, the tRNA-enriched fraction obtained from 5xFAD mice promoted abnormal dendritic arborization in cultured hippocampal neurons, and RTP801 silencing in the source neurons prevented this phenotype. Altogether, these results show that elevated RTP801 impairs RNA processing in vitro and in vivo in the context of AD and suggest that RTP801 inhibition could be a promising therapeutic approach.

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