Spliceosomal snRNA Epitranscriptomics

Morais, Pedro; Adachi, Hironori; Yu, Yi‐Tao

doi:10.3389/fgene.2021.652129

Cited by 81 publications

(71 citation statements)

References 145 publications

(204 reference statements)

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“…SnRNA is highly conserved, the content is small in cells, and the expression is spatiotemporally specific ( 29 ). After transcription according to the gene template, snRNA is transported out of the nucleus and combined with snRNA binding protein in the cytoplasm to form small nuclear ribonucleoproteins (snRNPs), which once again pass through the nuclear pore and enter the nucleus to become mature snRNA ( 30 ). The main function of snRNA is to participate in the splicing of RNA in cells, produce mature mRNA and rRNA, and regulate protein synthesis ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

Zhou

Wang

et al. 2022

Front. Immunol.

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Macrophages belong to a special phagocytic subgroup of human leukocytes and are one of the important cells of the human immune system. Small noncoding RNAs are a group of small RNA molecules that can be transcribed without the ability to encode proteins but could play a specific function in cells. SncRNAs mainly include microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs) and repeat RNAs. We used high-throughput sequencing analysis and qPCR to detect the expression changes of the small noncoding RNAome during macrophage polarization. Our results showed that 84 miRNAs and 47 miRNAs with were downregulated during M1 macrophage polarization and that 11 miRNAs were upregulated and 19 miRNAs were downregulated during M2 macrophage polarization. MiR-novel-3-nature and miR-27b-5p could promote expression of TNF-α which was marker gene of M1 macrophages. The piRNA analysis results showed that 69 piRNAs were upregulated and 61 piRNAs were downregulated during M1 macrophage polarization and that 3 piRNAs were upregulated and 10 piRNAs were downregulated during M2 macrophage polarization. DQ551351 and DQ551308 could promote the mRNA expression of TNF-α and DQ551351overexpression promoted the antitumor activity of M1 macrophages. SnoRNA results showed that 62 snoRNAs were upregulated and 59 snoRNAs were downregulated during M1 macrophage polarization, whereas 6 snoRNAs were upregulated and 10 snoRNAs were downregulated during M2 macrophage polarization. Overexpression of snoRNA ENSMUST00000158683.2 could inhibit expression of TNF-α. For snRNA, we found that 12 snRNAs were upregulated and 15 snRNAs were downregulated during M1 macrophage polarization and that 2 snRNAs were upregulated during M2 macrophage polarization. ENSMUSG00000096786 could promote expression of IL-1 and iNOS and ENSMUSG00000096786 overexpression promoted the antitumor activity of M1 macrophages. Analysis of repeat RNAs showed that 7 repeat RNAs were upregulated and 9 repeat RNAs were downregulated during M1 macrophage polarization and that 2 repeat RNAs were downregulated during M2 macrophage polarization. We first reported the expression changes of piRNA, snoRNA, snRNA and repeat RNA during macrophage polarization, and preliminarily confirmed that piRNA, snoRNA and snRNA can regulate the function of macrophages.

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Section: Introductionmentioning

confidence: 99%

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

Zhou

Wang

et al. 2022

Front. Immunol.

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“…U6 snRNA is the most highly conserved UsnRNA, reflecting its crucial roles at the active site of the spliceosome (Wilkinson et al, 2020). Different base modifications are found in each of the UsnRNAs, including U6 snRNA, but the role of these modifications is poorly understood (Morais et al, 2021). The essential ACAGA sequence of S. cerevisiae U6 snRNA is unmodified.…”

Section: Introductionmentioning

confidence: 99%

m⁶A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5’ splice site

Parker

Soanes

Kusakina

et al. 2022

Preprint

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Alternative splicing of messenger RNAs is associated with the evolution of developmentally complex eukaryotes. Splicing is mediated by the spliceosome, and docking of the pre-mRNA 5’ splice site into the spliceosome active site depends upon pairing with the conserved ACAGA sequence of U6 snRNA. In some species, including humans, the central adenosine of the ACAGA box is modified by N6 methylation, but the role of this m6A modification is poorly understood. Here we show that m6A modified U6 snRNA determines the accuracy and efficiency of splicing. We reveal that the conserved methyltransferase, FIO1, is required for Arabidopsis U6 snRNA m6A modification. Arabidopsis fio1 mutants show disrupted patterns of splicing that can be explained by the sequence composition of 5’ splice sites and cooperative roles for U5 and U6 snRNA in splice site selection. U6 snRNA m6A influences 3’ splice site usage and reinforces splicing fidelity at elevated temperature. We generalise these findings to reveal two major classes of 5’ splice site in diverse eukaryotes, which display anti-correlated interaction potential with U5 snRNA loop 1 and the U6 snRNA ACAGA box. We conclude that U6 snRNA m6A modification contributes to the selection of degenerate 5’ splice sites crucial to alternative splicing.

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“…They act as catalysts that splice mRNA into its mature form and they are important in the selection of alternative splicing sequences. 35 − 37 …”

Section: Types Of Naturally Occurring Rna and Their Functions In Biol...mentioning

confidence: 99%

The Progress and Promise of RNA Medicine─An Arsenal of Targeted Treatments

Tenchov

Zhou

2022

J. Med. Chem.

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In the past decade, there has been a shift in research, clinical development, and commercial activity to exploit the many physiological roles of RNA for use in medicine. With the rapid success in the development of lipid–RNA nanoparticles for mRNA vaccines against COVID-19 and with several approved RNA-based drugs, RNA has catapulted to the forefront of drug research. With diverse functions beyond the role of mRNA in producing antigens or therapeutic proteins, many classes of RNA serve regulatory roles in cells and tissues. These RNAs have potential as new therapeutics, with RNA itself serving as either a drug or a target. Here, based on the CAS Content Collection , we provide a landscape view of the current state and outline trends in RNA research in medicine across time, geography, therapeutic pipelines, chemical modifications, and delivery mechanisms.

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Spliceosomal snRNA Epitranscriptomics

Cited by 81 publications

References 145 publications

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

m⁶A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5’ splice site

The Progress and Promise of RNA Medicine─An Arsenal of Targeted Treatments

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Spliceosomal snRNA Epitranscriptomics

Cited by 81 publications

References 145 publications

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

m6A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5’ splice site

The Progress and Promise of RNA Medicine─An Arsenal of Targeted Treatments

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m⁶A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5’ splice site