Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity

Juárez, Ignacio; Su, Shi; Herbert, Zachary T.; Teijaro, John R.; Moulton, Vaishali R.

doi:10.3389/fimmu.2022.906355

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…To gain deeper insights into the role of m 6 A in biological progresses, it becomes imperative to discern transcriptome-wide m 6 A levels and sites within individual cells. For instance, the presence of a multitude of immune cell and T-cell subtypes [8][9][10][11] poses a formidable challenge, as current m 6 A detection methods designed for bulk cell populations fall short in characterizing m 6 A levels and sites at the single-cell level.…”

Section: Introductionmentioning

confidence: 99%

Scm⁶A: A fast and low-cost method for quantifying m⁶A modifications at the single-cell level

Li,

et al. 2023

Preprint

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It is widely accepted that m6A exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduce Scm6A, a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6Atransregulators andcissequence features, and found that Scm6A offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct m6A-seq analysis on CD4+and CD8+T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A’s reliability. We also used the scm6A-seq method to validate the reliability of our approach. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from COVID-19 patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A will have broad applications in the realm of m6A-related research.

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Section: Introductionmentioning

confidence: 99%

Scm⁶A: A fast and low-cost method for quantifying m⁶A modifications at the single-cell level

Li,

et al. 2023

Preprint

View full text Add to dashboard Cite

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Scm6A: A Fast and Low-cost Method for Quantifying m6A Modifications at the Single-cell Level

Li,

et al. 2024

Genomics, Proteomics &Amp; Bioinformatics

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It is widely accepted that N6-methyladenosine (m6A) exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduced Single-cell m6A Analysis (Scm6A), a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct N6-methyladenosine sequencing (m6A-seq) analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A’s reliability. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from the coronavirus disease 2019 (COVID-19) patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A have broad applications in the realm of m6A-related research.

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Autoregulated splicing of TRA2 β programs T cell fate in response to antigen-receptor stimulation

Karginov,

Ménoret,

Leclair

et al. 2024

Science

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T cell receptor (TCR) sensitivity to peptide–major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the RNA-binding protein (RBP) TRA2β in mouse and human. TRA2 β - PE splicing, seen during cancer and infection, was required for TCR-induced effector T cell expansion and function. Tra2 β-PE skipping enhanced T cell response to antigen by increasing TCR sensitivity. As antigen levels decreased, Tra2 β-PE reinclusion allowed T cell survival. Finally, we found that TRA2 β-PE was first included in the genome of jawed vertebrates that were capable of TCR gene rearrangements. We propose that TRA2 β - PE splicing acts as a gatekeeper of TCR sensitivity to shape T cell fate.

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Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity

Cited by 3 publications

References 34 publications

Scm⁶A: A fast and low-cost method for quantifying m⁶A modifications at the single-cell level

Scm⁶A: A fast and low-cost method for quantifying m⁶A modifications at the single-cell level

Scm6A: A Fast and Low-cost Method for Quantifying m6A Modifications at the Single-cell Level

Autoregulated splicing of TRA2 β programs T cell fate in response to antigen-receptor stimulation

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Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity

Cited by 3 publications

References 34 publications

Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level

Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level

Scm6A: A Fast and Low-cost Method for Quantifying m6A Modifications at the Single-cell Level

Autoregulated splicing of TRA2 β programs T cell fate in response to antigen-receptor stimulation

Contact Info

Product

Resources

About

Scm⁶A: A fast and low-cost method for quantifying m⁶A modifications at the single-cell level

Scm⁶A: A fast and low-cost method for quantifying m⁶A modifications at the single-cell level