Base-Resolution Sequencing Methods for Whole-Transcriptome Quantification of mRNA Modifications DOI Creative Commons
Lisheng Zhang, Qing Dai, Chuan He

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 57(1), P. 47 - 58

Published: Dec. 11, 2023

ConspectusRNA molecules are not merely a combination of four bases A, C, G, and U. Chemical modifications occur in almost all RNA species play diverse roles gene expression regulation. The abundant cellular RNAs, such as ribosomal (rRNA) transfer (tRNA), known to have the highest density modifications, which exert critical functions rRNA tRNA biogenesis, stability, subsequent translation. In recent years, on low-abundance mammalian cells, messenger (mRNA), regulatory noncoding (ncRNA), chromatin-associated (caRNA), been shown contain multiple different chemical with functional significance.As most mRNA modification mammals, N6-methyladenosine (m6A) affects nearly every stage processing metabolism, antibody-based m6A-MeRIP-seq (methylated immunoprecipitation sequencing) followed by high-throughput sequencing widely employed mapping m6A distribution transcriptome-wide biological systems. addition m6A, other pseudouridine (Ψ), 2′-O-methylation (Nm), 5-methylcytidine (m5C), internal N7-methylguanosine (m7G), N1-methyladenosine (m1A), N4-acetylcytidine (ac4C), etc. also exist polyA-tailed requiring effective approaches for whole-transcriptome profiling these non-m6A modifications. Like enrichment has primary method study distributions Methods more quantitatively map would dramatically improve our understanding marks RNA, thereby bettering informing implications. this Account, aimed at both single-base resolution fraction quantification, we summarize advances developing series chemistry- or biochemistry-based methods including Ψ, m5C, m1A, m7G, base resolution. These new methods, m6A-SAC-seq, eTAM-seq, BID-seq, UBS-seq, DAMM-seq, m1A-quant-seq, Nm-Mut-seq, m7G-quant-seq, promise conduct base-resolution major low input uncover dynamic changes stoichiometry during physiological processes, facilitating future investigations regulating potential biomarkers clinical diagnosis prognosis. quantitative allow limited sample requirements. same species, caRNA, ncRNA, nuclear nascent mitochondrial cell-free (cfRNA), etc., could be sequenced using methods.

Language: Английский

Alternative splicing and related RNA binding proteins in human health and disease DOI Creative Commons

Yining Tao,

Qi Zhang, Haoyu Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 2, 2024

Abstract Alternative splicing (AS) serves as a pivotal mechanism in transcriptional regulation, engendering transcript diversity, and modifications protein structure functionality. Across varying tissues, developmental stages, or under specific conditions, AS gives rise to distinct splice isoforms. This implies that these isoforms possess unique temporal spatial roles, thereby associating with standard biological activities diseases. Among these, AS-related RNA-binding proteins (RBPs) play an instrumental role regulating alternative events. Under physiological the diversity of mediated by influences structure, function, interaction, localization proteins, participating differentiation development array tissues organs. pathological alterations are linked various diseases, particularly cancer. These changes can lead gene patterns, culminating loss For instance, cancer, abnormalities RBPs may result aberrant expression cancer-associated genes, promoting onset progression tumors. also associated numerous neurodegenerative diseases autoimmune Consequently, study across different holds significant value. review provides detailed account recent advancements tissue which aids deepening understanding complexity offers new insights methodologies for precision medicine.

Language: Английский

Citations

88
Emerging Roles of RNA Methylation in Development DOI
Mengke Wang, Chun‐Chun Gao, Yun‐Gui Yang

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3417 - 3427

Published: Nov. 15, 2023

More than 170 different types of chemical modifications have been identified on diverse RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) ubiquitous post-transcriptional modification are widely involved in regulating metabolic processes such RNA degradation, translation, stability, export, mediating important physiological pathological stress regulation, immune response, development, tumorigenesis. Recently, regulatory role during developmental is getting more attention. Therefore, development low-input even single-cell high-resolution sequencing technologies crucial for exploration roles these biological events trace samples.This account focuses various processes. We describe distribution characteristics modifications, catalytic enzymes, binding proteins, technologies. dynamically reversible, which can be catalyzed by methyltransferases eliminated demethylases. m6A most abundant eukaryote mRNA, mainly concentrated near stop codon, involves metabolism regulation. m5C, another studied modification, has a organisms species, enriched regions downstream translation initiation sites broadly distributes across whole coding sequence (CDS) mammalian mRNAs. m1A, with lower abundance m6A, distributed types, locates 5' untranslated region (5'UTR) mRNA regulates translation. m7G, one common eukaryotes, at cap internal positions RNAs recently gained considerable attention.Thanks to technology, found regulate tumorigenic process, including tumor proliferation, invasion, metastasis modulating oncogenes suppressor genes, affect oocyte maturation embryonic through maternal zygotic genes. m5C related proteins participate plant growth, neural stem cell differentiation dependent manner. m1A also revealed m7G dysregulation neurodevelopmental disorders neurodegenerative diseases.Collectively, we summarized gradually exhibited methylation discussed possibility candidate biomarkers potential therapeutic targets. The technological anticipated major driving force expand our knowledge this field.

Language: Английский

Citations

30
M7G modification of FTH1 and pri-miR-26a regulates ferroptosis and chemotherapy resistance in osteosarcoma DOI
Mingyu He, Yang Wang,

Jiajie Xie

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 43(5), P. 341 - 353

Published: Dec. 1, 2023

Language: Английский

Citations

26
Critical roles and clinical perspectives of RNA methylation in cancer DOI Creative Commons

Ganglei Li,

Qinfan Yao,

Peixi Liu

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract RNA modification, especially methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all modifications. It plays significant role in metabolism, affecting processing, stability, translation, thereby modulating gene expression cell essential proliferation, survival, metastasis. Increasing studies have revealed the disruption metabolism mediated by methylation has been implicated various aspects cancer particularly metabolic reprogramming immunity. This profound implications tumor growth, metastasis, therapy response. Herein, we elucidate fundamental characteristics their impact on expression. We highlight intricate relationship between reprogramming, immunity, using well‐characterized phenomenon as framework to discuss methylation's specific roles mechanisms progression. Furthermore, explore potential targeting regulators novel approach therapy. By underscoring complex which contributes this review provides foundation developing new prognostic markers therapeutic strategies aimed at treatment.

Language: Английский

Citations

17
Cancer plasticity in therapy resistance: Mechanisms and novel strategies DOI

Xing Niu,

Wenjing Liu,

Zhang Yinling

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 76, P. 101114 - 101114

Published: June 22, 2024

Language: Английский

Citations

17
The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9‐Mediated Splicing of NFATc4 DOI Creative Commons
Shuting Yu,

ZhiYong Sun,

Tiantian Ju

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(29)

Published: May 29, 2024

Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1-catalyzed RNA N7-methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 mechanism underlying non-ischemic HF. It found that upregulated human failing hearts hypertrophic murine following transverse aortic constriction (TAC) Angiotensin II (Ang II) infusion. YY1 acts as transcriptional for during hypertrophy. knockout alleviates dysfunction upon pressure overload from TAC or Ang stimulation. Conversely, cardiac-specific overexpression results remodeling. Mechanically, increases SRSF9 expression by inducing m7G mRNA, facilitating alternative splicing stabilization NFATc4, thereby promoting Moreover, knockdown protects against TAC- Mettl1-induced phenotypes vivo vitro. The identifies crucial regulator hypertrophy, providing novel therapeutic target

Language: Английский

Citations

14
M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets DOI Creative Commons
Mengzhen Han,

Qibo Huang,

Xinxin Li

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1238 - 1255

Published: Jan. 1, 2024

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level.Among these modifications, N7-methylguanosine (m7G) stands out as one of most prevalent.Over recent years, significant attention has been directed towards understanding implications m7G modification.This modification is present diverse molecules, including transfer RNAs, messenger ribosomal other noncoding RNAs.Its regulation occurs through series specific methyltransferases m7G-binding proteins.Notably, implicated various diseases, prominently across multiple cancer types.Earlier studies have elucidated significance context immune within tumor microenvironment.This comprehensive review culminates synthesis findings related to modulation cells infiltration, encompassing T cells, B innate all orchestrated modification.Furthermore, interplay between its regulatory proteins can profoundly affect efficacy adjuvant therapeutics, thereby potentially serving biomarker therapeutic target for combinatory interventions types.

Language: Английский

Citations

12
Beyond reader proteins: RNA binding proteins and RNA modifications in conversation to regulate gene expression DOI
Christian Fagre,

Wendy V. Gilbert

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(2)

Published: March 1, 2024

Abstract Post‐transcriptional mRNA modifications play diverse roles in gene expression and RNA function. In many cases, function by altering how cellular machinery such as binding proteins (RBPs) interact with substrates. For instance, N6‐methyladenosine (m6A) is recognized the well‐characterized YTH domain‐containing family of “reader” proteins. other modifications, similar global readers modification status have not been clearly defined. Rather, most interactions between RBPs a more complicated dependence on sequence context modality. The current handful studies that demonstrate impacting protein likely represent only fraction full landscape. this review, we dissect known instances RBP binding, specifically m6A, N1‐methyladenosine (m1A), 5‐methylcytosine (m5C), pseudouridine (Ψ), internal N7‐methylguanosine. We then review biochemical properties these identified including dihydrouridine (D), N4 ‐ acetylcytosine (ac4C), 2′‐O‐Methylation (Nme). focus would be to impact RNA:RBP interactions, changes hydrogen bond potential, base‐stacking efficiency, conformational preferences. effects secondary structure well‐studied, briefly discuss structural imparted can lead changes. Finally, strategies for uncovering as‐yet‐to‐be modification‐sensitive RBP:RNA Interactions. Coordinating future efforts intersect epitranscriptome RNA–protein interactome will illuminate rules governing recognition mechanisms responsible biological consequences modification. This article categorized under: Structure Dynamics > Structure, Chemistry Interactions Proteins Other Molecules Protein‐RNA Recognition Processing Editing Modification

Language: Английский

Citations

11
Dynamic RNA methylation modifications and their regulatory role in mammalian development and diseases DOI
Wenlan Yang, Yongliang Zhao, Yun‐Gui Yang

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Language: Английский

Citations

10
Cellular responses to RNA damage DOI Creative Commons
Jacqueline Cordes,

Shubo Zhao,

Christoph Engel

et al.

Cell, Journal Year: 2025, Volume and Issue: 188(4), P. 885 - 900

Published: Feb. 1, 2025

RNA plays a central role in protein biosynthesis and performs diverse regulatory catalytic functions, making it essential for all processes of life. Like DNA, is constantly subjected to damage from endogenous environmental sources. However, while the DNA response has been extensively studied, was long assumed that lesions are relatively inconsequential due transient nature most molecules. Here, we review recent studies challenge this view by revealing complex responses determine survival when cells exposed nucleic acid-damaging agents promote resolution lesions.

Language: Английский

Citations

2