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Increasing MicroRNA Abundance by Targeting Biogenesis from the Primary Transcript with Steric-Blocking Antisense Oligonucleotides 利用立体阻断反义寡核苷酸靶向初级转录本的生物生成,提高 MicroRNA 的丰度
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-09-10 DOI: 10.1261/rna.080021.124
Mallory A Havens, Anthony J Hinrich, Frank Rigo, Michelle L Hastings
MicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs. ASOs have been less explored as a tool to elevate miRNA levels, which could also be beneficial for treating disease. In this study, using the PKD1/miR-1225 gene locus as an example, where miR-1225 is located within a PKD1 intron, we demonstrate an ASO-based strategy that increases miRNA abundance by enhancing biogenesis from the primary miRNA transcript. Disruptions in PKD1 and miR-1225 are associated with autosomal dominant polycystic kidney disease (ADPKD) and various cancers, respectively, making them important therapeutic targets. We investigated PKD1 sequence variants reported in ADPKD that are located within the sequence shared by miR-1225 and PKD1, and identified one that causes a reduction in miR-1225 without affecting PKD1. We show that this reduction in miR-1225 can be recovered by treatment with a steric-blocking ASO. The ASO-induced increase in miR-1225 correlates with a decrease in the abundance of predicted miR-1225 cellular mRNA targets. This study demonstrates that miRNA abundance can be elevated using ASOs targeted to the primary transcript. This steric-blocking ASO-based approach has broad potential application as a therapeutic strategy for diseases that could be treated by modulating miRNA biogenesis.
微RNA(miRNA)是基因表达的调控因子,它们的失调与癌症和其他疾病有关,因此成为重要的治疗靶标。目前正在探索几种靶向和调节 miRNA 活性的策略。例如,立体阻断反义寡核苷酸(ASO)可通过阻断特定 mRNA 的结合位点或与 miRNA 本身碱基配对来阻止其与靶 mRNA 的相互作用,从而降低 miRNA 的活性。作为一种提高 miRNA 水平的工具,ASOs 的研究较少,而提高 miRNA 水平也可能有益于治疗疾病。在本研究中,以 miR-1225 位于 PKD1 内含子中的 PKD1/miR-1225 基因位点为例,我们展示了一种基于 ASO 的策略,这种策略通过增强主要 miRNA 转录本的生物生成来提高 miRNA 丰度。PKD1 和 miR-1225 的紊乱分别与常染色体显性多囊肾病(ADPKD)和各种癌症有关,因此成为重要的治疗靶点。我们研究了 ADPKD 中报道的位于 miR-1225 和 PKD1 共享序列内的 PKD1 序列变异,并发现了一种导致 miR-1225 减少而不影响 PKD1 的变异。我们的研究表明,这种 miR-1225 的减少可以通过使用立体阻断型 ASO 来恢复。ASO 诱导的 miR-1225 的增加与预测的 miR-1225 细胞 mRNA 靶标丰度的降低相关。这项研究表明,使用针对主转录本的 ASO 可以提高 miRNA 的丰度。这种基于立体阻断 ASO 的方法具有广泛的潜在应用前景,可作为一种治疗策略,通过调节 miRNA 的生物发生来治疗疾病。
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引用次数: 0
tRNAVal allows four-way decoding with unmodified uridine at the wobble position in Lactobacillus casei 在干酪乳杆菌中,tRNAVal 可与位于摆动位置的未修饰尿苷进行四向解码
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-09-10 DOI: 10.1261/rna.080155.124
Riko Sugita, Vincent Guérineau, David Touboul, Satoko Yoshizawa, Kazuyuki Takai, Chie Tomikawa
Modifications at the wobble position (position 34) of tRNA facilitate interactions that enable or stabilize non-Watson-Crick basepairs. In bacterial tRNA, 5-hydroxyuridine (ho5U) derivatives xo5U [x: methyl (mo5U), carboxymethyl (cmo5U), and methoxycarbonylmethyl (mcmo5U)] present at the wobble positions of tRNAs are responsible for recognition of NYN codon families. These modifications of U34 allow basepairing not only with A and G but also with U and in some cases C. mo5U was originally found in Gram-positive bacteria, and cmo5U and mcmo5U were found in Gram-negative bacteria. tRNAs of Mycoplasma species, mitochondria, and chloroplasts adopt four-way decoding in which unmodified U34 recognizes codons ending in A, G, C, and U. Lactobacillus casei, Gram-positive bacteria and lactic acid bacteria, lacks the modification enzyme genes for xo5U biosynthesis. Nevertheless, L. casei has only one type of tRNAVal with the anticodon UAC [tRNAVal(UAC)]. However, the genome of L. casei encodes an undetermined tRNA (tRNAUnd) gene, and the sequence corresponding to the anticodon region is GAC. Here, we confirm that U34 in L. casei tRNAVal is unmodified and that there is no tRNAUnd expression in the cells. In addition, in vitro transcribed tRNAUnd was not aminoacylated by L. casei valyl-tRNA synthetase suggesting that tRNAUnd is not able to accept valine, even if expressed in cells. Correspondingly, native tRNAVal(UAC) with unmodified U34 bound to all four valine codons in the ribosome A site. This suggests that L. casei tRNAVal decodes all valine codons by four-way decoding, similarly to tRNAs from Mycoplasma species, mitochondria, and chloroplasts.
tRNA 的摆动位置(第 34 位)上的修饰有助于产生或稳定非沃森克里克碱基对的相互作用。在细菌 tRNA 中,tRNA 的摆动位置上的 5-羟基尿苷(ho5U)衍生物 xo5U [x:甲基(mo5U)、羧甲基(cmo5U)和甲氧羰基甲基(mcmo5U)]负责识别 NYN 密码子家族。mo5U 最初出现在革兰氏阳性细菌中,而 cmo5U 和 mcmo5U 则出现在革兰氏阴性细菌中。支原体、线粒体和叶绿体的 tRNA 采用四向解码,其中未修饰的 U34 可识别以 A、G、C 和 U 结尾的密码子。革兰氏阳性菌和乳酸菌干酪乳杆菌缺乏用于 xo5U 生物合成的修饰酶基因。不过,干酪乳杆菌只有一种反密码子为 UAC 的 tRNAVal [tRNAVal(UAC)]。然而,干酪乳杆菌的基因组编码一种未确定的 tRNA(tRNAUnd)基因,其反密码子区域对应的序列是 GAC。在此,我们证实 L. casei tRNAVal 中的 U34 未被修饰,细胞中没有 tRNAUnd 表达。此外,体外转录的 tRNAUnd 不能被 L. casei 缬氨酰-tRNA 合成酶氨基化,这表明 tRNAUnd 即使在细胞中表达,也不能接受缬氨酸。相应地,未修饰 U34 的原生 tRNAVal(UAC) 与核糖体 A 位点的所有四个缬氨酸密码子结合。这表明 L. casei tRNAVal 通过四向解码对所有缬氨酸密码子进行解码,与来自支原体、线粒体和叶绿体的 tRNA 相似。
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引用次数: 0
Regulatory Interplay Between SR Proteins Governs CLK1 Kinase Splice Variants Production SR蛋白之间的调控相互作用控制着CLK1激酶剪接变体的产生
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-09-09 DOI: 10.1261/rna.080107.124
Lulzim Shkreta, Aurelie Delannoy, Johanne Toutant, Benoit Chabot
The CLK1 kinase phosphorylates SR proteins to modulate their splicing regulatory activity. Skipping of alternative exon 4 on the CLK1 pre-mRNA produces a CLK1 variant lacking the catalytic site. Here, we aimed to understand how various SR proteins integrate into the regulatory program that controls CLK1 exon 4 splicing. Previously, we observed that the depletion of SRSF10 promoted the inclusion of CLK1 exon 4. Using expression of tagged proteins and CRISPR/Cas9-mediated knockouts in HCT116 cells, we now identify TRA2b, TRA2a, SRSF4, SRSF5, SRSF7, SRSF8 and SRSF9 as activators of exon 4 inclusion. In contrast, SRSF3, SRSF10 and SRSF12 elicit exon 4 skipping. Using CRISPR/dCas13Rx and RNA immunoprecipitation assays, we map an enhancer in exon 4 interacting with TRA2b. Notably, CLK1 kinase inhibitors antagonized the repressor activity of HA-SRSF10, HA-SRSF12 and HA-SRSF3. Our results suggest that CLK1 exon 4 inclusion is determined primarily by a balance between the activities of TRA2 proteins and CLK-phosphorylated SRSF3. CLK-phosphorylated SRSF10 and SRSF12 would interact with TRA2 proteins to prevent their enhancer activity, allowing SRSF3 to enforce exon 4 skipping more efficiently. Our study provides insight into the complex regulatory network controlling the alternative splicing of CLK1, which uses CLK1-mediated phosphorylation of SR proteins to regulate the inclusion of catalytic exon 4 in CLK1 transcripts.
CLK1 激酶将 SR 蛋白磷酸化,以调节其剪接调节活性。跳过CLK1前mRNA上的替代外显子4会产生缺乏催化位点的CLK1变体。在这里,我们旨在了解各种 SR 蛋白如何整合到控制 CLK1 第 4 号外显子剪接的调控程序中。此前,我们观察到 SRSF10 的缺失促进了 CLK1 第 4 外显子的包含。通过在 HCT116 细胞中表达标记蛋白和 CRISPR/Cas9 介导的基因敲除,我们现在确定 TRA2b、TRA2a、SRSF4、SRSF5、SRSF7、SRSF8 和 SRSF9 是外显子 4 包含的激活因子。与此相反,SRSF3、SRSF10 和 SRSF12 会引起外显子 4 跳过。利用 CRISPR/dCas13Rx 和 RNA 免疫沉淀测定,我们绘制了与 TRA2b 相互作用的第 4 外显子增强子图。值得注意的是,CLK1激酶抑制剂拮抗了HA-SRSF10、HA-SRSF12和HA-SRSF3的抑制活性。我们的研究结果表明,CLK1 第 4 外显子的包含主要由 TRA2 蛋白和 CLK 磷酸化 SRSF3 的活性之间的平衡决定。CLK磷酸化的SRSF10和SRSF12会与TRA2蛋白相互作用,阻止它们的增强子活性,从而使SRSF3更有效地执行外显子4的跳过。我们的研究深入揭示了控制 CLK1 替代剪接的复杂调控网络,该网络利用 CLK1 介导的 SR 蛋白磷酸化来调控 CLK1 转录本中催化外显子 4 的包含。
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引用次数: 0
Corrigendum: Gene regulation by a glycine riboswitch singlet uses a finely tuned energetic landscape for helical switching 更正:甘氨酸核糖开关单体利用微调的能量景观进行螺旋切换的基因调控
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-09-01 DOI: 10.1261/rna.080151.124
Chad D. Torgerson, David A. Hiller, Shira Stav, Scott A. Strobel
RNA 24: 1813–1827 (2018)
RNA 24: 1813-1827 (2018)
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引用次数: 0
Corrigendum: Translation regulation by a guanidine-II riboswitch is highly tunable in sensitivity, dynamic range, and apparent cooperativity 更正:鸟苷-II 核糖开关的翻译调控在灵敏度、动态范围和明显的合作性方面具有高度可调性
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-09-01 DOI: 10.1261/rna.080150.124
Caroline M. Focht, David A. Hiller, Sabrina G. Grunseich, Scott A. Strobel
RNA 29: 1126–1139 (2023)
RNA 29: 1126-1139 (2023)
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引用次数: 0
Adenosine modifications impede SARS-CoV-2 RNA-dependent RNA transcription. 腺苷修饰阻碍了 SARS-CoV-2 RNA 依赖性 RNA 转录。
IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-08-16 DOI: 10.1261/rna.079991.124
Laura R Snyder, Ingrid Kilde, Artem Nemudryi, Blake Wiedenheft, Markos Koutmos, Kristin S Koutmou

SARS-CoV-2, the causative virus of the COVID-19 pandemic, follows SARS and MERS as recent zoonotic coronaviruses causing severe respiratory illness and death in humans. The recurrent impact of zoonotic coronaviruses demands a better understanding of their fundamental molecular biochemistry. Nucleoside modifications, which modulate many steps of the RNA life cycle, have been found in SARS-CoV-2 RNA, although whether they confer a pro- or antiviral effect is unknown. Regardless, the viral RNA-dependent RNA polymerase will encounter these modifications as it transcribes through the viral genomic RNA. We investigated the functional consequences of nucleoside modification on the pre-steady state kinetics of SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted transcription system with modified RNA templates. Our findings show that N 6-methyladenosine and 2'-O-methyladenosine modifications slow the rate of viral transcription at magnitudes specific to each modification, which has the potential to impact SARS-CoV-2 genome maintenance.

SARS-CoV-2 是 COVID-19 大流行的致病病毒,它是继 SARS 和 MERS 之后又一种导致人类严重呼吸道疾病和死亡的人畜共患冠状病毒。人畜共患冠状病毒的反复影响要求我们更好地了解其基本的分子生物化学性质。在 SARS-CoV-2 RNA 中发现了核苷修饰,这种修饰可调节 RNA 生命周期的许多步骤,但它们是否具有促进或抗病毒作用尚不清楚。无论如何,病毒 RNA 依赖性 RNA 聚合酶在转录病毒基因组 RNA 时都会遇到这些修饰。我们利用体外重组转录系统和修饰的 RNA 模板,研究了核苷修饰对 SARS-CoV-2 RNA 依赖性 RNA 转录前稳态动力学的功能影响。我们的研究结果表明,N6-甲基腺苷和 2'O-甲基腺苷修饰会减慢病毒转录的速度,而每种修饰的程度各不相同,这可能会影响 SARS-CoV-2 基因组的维持。
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引用次数: 0
Structure and sequence at an RNA template 5' end influence insertion of transgenes by an R2 retrotransposon protein. RNA 模板 5' 端的结构和序列会影响 R2 逆转录质子蛋白插入转基因。
IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-08-16 DOI: 10.1261/rna.080031.124
Sarah M Palm, Connor A Horton, Xiaozhu Zhang, Kathleen Collins

R2 non-long terminal repeat retrotransposons insert site-specifically into ribosomal RNA genes (rDNA) in a broad range of multicellular eukaryotes. R2-encoded proteins can be leveraged to mediate transgene insertion at 28S rDNA loci in cultured human cells. This strategy, precise RNA-mediated insertion of transgenes (PRINT), relies on the codelivery of an mRNA encoding R2 protein and an RNA template encoding a transgene cassette of choice. Here, we demonstrate that the PRINT RNA template 5' module, which as a complementary DNA 3' end will generate the transgene 5' junction with rDNA, influences the efficiency and mechanism of gene insertion. Iterative design and testing identified optimal 5' modules consisting of a hepatitis delta virus-like ribozyme fold with high thermodynamic stability, suggesting that RNA template degradation from its 5' end may limit transgene insertion efficiency. We also demonstrate that transgene 5' junction formation can be either precise, formed by annealing the 3' end of first-strand complementary DNA with the upstream target site, or imprecise, by end-joining, but this difference in junction formation mechanism is not a major determinant of insertion efficiency. Sequence characterization of imprecise end-joining events indicates surprisingly minimal reliance on microhomology. Our findings expand the current understanding of the role of R2 retrotransposon transcript sequence and structure, and especially the 5' ribozyme fold, for retrotransposon mobility and RNA-templated gene synthesis in cells.

在多种多细胞真核生物中,R2 非长末端重复反转座子会特异性地插入核糖体 RNA 基因(rDNA)。在培养的人类细胞中,R2-编码的蛋白质可用于介导转基因插入 28S rDNA 基因座。这种名为 "精确 RNA 介导的转基因插入"(PRINT)的策略依赖于编码 R2 蛋白的 mRNA 和编码转基因盒的 RNA 模板的共同传递。在这里,我们证明了 PRINT RNA 模板 5' 模块(作为互补 DNA 3' 端将产生转基因 5' 与 rDNA 的连接)会影响基因插入的效率和机制。迭代设计和测试确定了最佳的 5'模块,该模块由热力学稳定性高的类似肝炎病毒的核酶折叠组成,这表明 RNA 模板 5'端的降解可能会限制转基因的插入效率。我们还证明,转基因 5' 连接的形成既可以是精确的,即通过第一链互补 DNA 的 3' 端与上游目标位点退火形成,也可以是不精确的,即通过末端连接形成,但连接形成机制的这种差异并不是决定插入效率的主要因素。对不精确末端连接事件的序列特征分析表明,对微组构的依赖程度出奇地低。我们的研究结果拓展了目前对 R2 逆转录子转录本序列和结构,特别是 5' 核糖酶折叠在细胞内逆转录子移动性和 RNA 模板基因合成中的作用的认识。
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引用次数: 0
Discrete measurements of RNA polymerase and reverse transcriptase fidelity reveal evolutionary tuning. 对 RNA 聚合酶和逆转录酶保真度的离散测量揭示了进化调整。
IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-08-16 DOI: 10.1261/rna.080002.124
Vladimir Potapov, Stanislas Krudup, Sean Maguire, Irem Unlu, Shengxi Guan, Jackson A Buss, Benedict A Smail, Trevor van Eeuwen, Martin S Taylor, Kathleen H Burns, Jennifer L Ong, Robert J Trachman

Direct methods for determining the fidelity of DNA polymerases are robust, with relatively little sample manipulation before sequencing. In contrast, methods for measuring RNA polymerase and reverse transcriptase fidelities are complicated by additional preparation steps that introduce ambiguity and error. Here, we describe a sequencing method, termed Roll-Seq, for simultaneously determining the individual fidelities of RNA polymerases and reverse transcriptases (RT) using Pacific Biosciences single molecule real-time sequencing. By using reverse transcriptases with high rolling-circle activity, Roll-Seq generates long concatemeric cDNA from a circular RNA template. To discern the origin of a mutation, errors are recorded and determined to occur within a single concatemer (reverse transcriptase error) or all concatemers (RNA polymerase error) over the cDNA strand. We used Roll-Seq to measure the fidelities of T7 RNA polymerases, a Group II intron-encoded RT (Induro), and two LINE RTs (Fasciolopsis buski R2-RT and human LINE-1). Substitution rates for Induro and R2-RT are the same for cDNA and second-strand synthesis while LINE-1 has 2.5-fold lower fidelity when performing second-strand synthesis. Deletion and insertion rates increase for all RTs during second-strand synthesis. In addition, we find that a structured RNA template impacts fidelity for both RNA polymerase and RT. The accuracy and precision of Roll-Seq enable this method to be applied as a complementary analysis to structural and mechanistic characterization of RNA polymerases and reverse transcriptases or as a screening method for RNAP and RT fidelity.

测定 DNA 聚合酶保真度的直接方法非常可靠,在测序前对样本的处理相对较少。相比之下,测量 RNA 聚合酶和反转录酶保真度的方法却因额外的制备步骤而变得复杂,从而带来了模糊性和误差。在这里,我们介绍了一种测序方法(称为 Roll-Seq),利用太平洋生物科学公司的单分子实时测序技术,同时测定 RNA 聚合酶和反转录酶(RT)各自的保真度。通过使用具有高滚动圆活性的反转录酶,Roll-Seq 能从环状 RNA 模板中生成长的串联 cDNA。为了辨别突变的起源,需要记录并确定错误发生在 cDNA 链上的单个连接子(反转录酶错误)或所有连接子(RNA 聚合酶错误)。我们使用 Roll-Seq 测量了 T7 RNA 聚合酶、第二类内含子编码 RT(Induro)和两种 LINE RT(Fasciolopsis buski R2-RT 和人类 LINE-1)的保真度。Induro 和 R2-RT 在 cDNA 和第二链合成中的替换率相同,而 LINE-1 在进行第二链合成时的保真度要低 2.5 倍。在第二链合成过程中,所有 RT 的删除率和插入率都会增加。此外,我们还发现结构化 RNA 模板会影响 RNA 聚合酶和 RT 的保真度。Roll-Seq 的准确性和精确性使这种方法可以作为 RNA 聚合酶和逆转录酶结构和机理特征分析的补充分析,或作为 RNAP 和 RT 保真度的筛选方法。
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引用次数: 0
Loss of ADAR1 protein induces changes in small RNA landscape in hepatocytes. ADAR1 蛋白的缺失会诱导肝细胞中的小 RNA 结构发生变化。
IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-08-16 DOI: 10.1261/rna.080097.124
Kristina Roučová, Václav Vopálenský, Tomáš Mašek, Edgar Del Llano, Jan Provazník, Jonathan J M Landry, Nayara Azevedo, Edvard Ehler, Vladimír Beneš, Martin Pospíšek

In recent years, numerous evidence has been accumulated about the extent of A-to-I editing in human RNAs and the key role ADAR1 plays in the cellular editing machinery. It has been shown that A-to-I editing occurrence and frequency are tissue-specific and essential for some tissue development, such as the liver. To study the effect of ADAR1 function in hepatocytes, we have created Huh7.5 ADAR1 KO cell lines. Upon IFN treatment, the Huh7.5 ADAR1 KO cells show rapid arrest of growth and translation, from which they do not recover. We analyzed translatome changes by using a method based on sequencing of separate polysome profile RNA fractions. We found significant changes in the transcriptome and translatome of the Huh7.5 ADAR1 KO cells. The most prominent changes include negatively affected transcription by RNA polymerase III and the deregulation of snoRNA and Y RNA levels. Furthermore, we observed that ADAR1 KO polysomes are enriched in mRNAs coding for proteins pivotal in a wide range of biological processes such as RNA localization and RNA processing, whereas the unbound fraction is enriched mainly in mRNAs coding for ribosomal proteins and translational factors. This indicates that ADAR1 plays a more relevant role in small RNA metabolism and ribosome biogenesis.

近年来,关于人类 RNA 中 A 到 I 编辑的程度以及 ADAR1 在细胞编辑机制中的关键作用,已经积累了大量证据。研究表明,A-to-I 编辑的发生和频率具有组织特异性,对某些组织(如肝脏)的发育至关重要。为了研究 ADAR1 功能对肝细胞的影响,我们创建了 Huh7.5 ADAR1 KO 细胞系。经 IFN 处理后,Huh7.5 ADAR1 KO 细胞的生长和翻译迅速停止,且无法恢复。我们采用了一种基于单独多聚核糖体轮廓 RNA 片段测序的方法来分析翻译组的变化。我们发现 Huh7.5 ADAR1 KO 细胞的转录组和翻译组发生了明显变化。最突出的变化包括 RNA 聚合酶 III 的转录受到负面影响以及 snoRNA 和 Y RNA 水平的失调。此外,我们还观察到,ADAR1 KO 多聚体富含编码 RNA 定位和 RNA 处理等多种生物过程中关键蛋白的 mRNA,而未结合部分则主要富含编码核糖体蛋白和翻译因子的 mRNA。这表明 ADAR1 在小 RNA 代谢和核糖体生物发生过程中发挥着更重要的作用。
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引用次数: 0
Function and mechanism of action of the small regulatory RNA ArcZ in Enterobacterales. 肠杆菌小调控 RNA ArcZ 的功能和作用机制
IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA
Pub Date : 2024-08-16 DOI: 10.1261/rna.080010.124
Quentin Dubois, Typhaine Brual, Charlotte Oriol, Pierre Mandin, Guy Condemine, Erwan Gueguen

ArcZ is a small regulatory RNA conserved in Enterobacterales It is an Hfq-dependent RNA that is cleaved by RNase E in a processed form of 55-60 nucleotides. This processed form is highly conserved for controlling the expression of target mRNAs. ArcZ expression is induced by abundant oxygen levels and reaches its peak during the stationary growth phase. This control is mediated by the oxygen-responsive two-component system ArcAB, leading to the repression of arcZ transcription under low-oxygen conditions in most bacteria in which it has been studied. ArcZ displays multiple targets, and it can control up to 10% of a genome and interact directly with more than 300 mRNAs in Escherichia coli and Salmonella enterica ArcZ displays a multifaceted ability to regulate its targets through diverse mechanisms such as RNase recruitment, modulation of ribosome accessibility on the mRNA, and interaction with translational enhancing regions. By influencing stress response, motility, and virulence through the regulation of master regulators such as FlhDC or RpoS, ArcZ emerges as a major orchestrator of cell physiology within Enterobacterales.

ArcZ 是一种在肠杆菌中保守存在的小型调控 RNA,它是一种依赖于 Hfq 的 RNA,被 RNase E 分解为 55 至 60 个核苷酸的加工形式。这种加工形式在控制目标 mRNA 的表达方面高度保守。ArcZ 的表达受丰富氧气水平的诱导,并在静止生长阶段达到峰值。这种控制是由氧响应双组分系统 ArcAB 介导的,导致在研究过的大多数细菌中,arcZ 在低氧条件下的转录受到抑制。在大肠杆菌和肠炎沙门氏菌中,ArcZ 可控制多达 10%的基因组,并与 300 多种 mRNA 直接相互作用。 ArcZ 可通过多种机制(如 RNase 招募、调节 mRNA 上核糖体的可及性以及与翻译增强区的相互作用)对其目标进行多方面的调控。ArcZ 通过调控 FlhDC 或 RpoS 等主调控因子影响应激反应、运动性和毒力,成为肠杆菌内细胞生理学的主要协调者。
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引用次数: 0
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RNA
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