Interconnections between m6A RNA modification, RNA structure, and protein–RNA complex assembly DOI Creative Commons
Simone Höfler, Olivier Duss

Life Science Alliance, Journal Year: 2023, Volume and Issue: 7(1), P. e202302240 - e202302240

Published: Nov. 7, 2023

Protein-RNA complexes exist in many forms within the cell, from stable machines such as ribosome to transient assemblies like spliceosome. All protein-RNA rely on spatially and temporally coordinated interactions between specific proteins RNAs achieve a functional form. RNA folding structure are often critical for successful protein binding complex formation. modifications change chemical nature of given alter its kinetics. Both these alterations can affect how if or other interact with modified assemble into complexes. N

Language: Английский

The role of RNA methylation in tumor immunity and its potential in immunotherapy DOI Creative Commons
Yan Li,

Haoer Jin,

Qingling Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

Citations

32
Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

18
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
Persistent organic pollutant perfluorooctanoic acid induces alterations in epigenetic modifications of DNA and RNA DOI

Shu-Yi Gu,

Tian Feng,

Fang‐Yin Gang

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110957 - 110957

Published: Feb. 1, 2025

Language: Английский

Citations

4
Charting the epitranscriptomic landscape across RNA biotypes using native RNA nanopore sequencing DOI
Gregor Diensthuber, Eva Maria Novoa

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 276 - 289

Published: Jan. 1, 2025

Language: Английский

Citations

2
Inflammation in cancer: therapeutic opportunities from new insights DOI Creative Commons
Yifei Xie, Fangfang Liu, Yunfei Wu

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 24, 2025

As one part of the innate immune response to external stimuli, chronic inflammation increases risk various cancers, and tumor-promoting is considered enabling characteristics cancer development. Recently, there has been growing evidence on role anti-inflammation therapy in prevention treatment. And researchers have already achieved several noteworthy outcomes. In review, we explored underlying mechanisms by which affects occurrence development cancer. The pro- or anti-tumor effects these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, extracellular matrix are discussed. Since FDA-approved drugs like aspirin show obvious effects, unique advantages due their relatively fewer side with long-term use compared chemotherapy drugs. make them promising candidates for chemoprevention. Overall, this review discusses molecules carcinogenesis new molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that expected be applied clinical practice, well recent discoveries effect non-steroidal anti-inflammatory steroidal disadvantages application chemoprevention also

Language: Английский

Citations

2
m6A-driven SF3B1 translation control steers splicing to direct genome integrity and leukemogenesis DOI Creative Commons
Maciej Cieśla, Phuong Cao Thi Ngoc, Sowndarya Muthukumar

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(7), P. 1165 - 1179.e11

Published: March 20, 2023

SF3B1 is the most mutated splicing factor (SF) in myelodysplastic syndromes (MDSs), which are clonal hematopoietic disorders with variable risk of leukemic transformation. Although tumorigenic mutations have been extensively characterized, role "non-mutated" wild-type cancer remains largely unresolved. Here, we identify a conserved epitranscriptomic program that steers levels to counteract leukemogenesis. Our analysis human and murine pre-leukemic MDS cells reveals dynamic regulation protein abundance, affects MDS-to-leukemia progression vivo. Mechanistically, ALKBH5-driven 5′ UTR m6A demethylation fine-tunes translation directing central DNA repair epigenetic regulators during This impacts genome stability leukemia vivo, supporting an integrative humans molecular signatures may predict mutational variability poor prognosis. These findings highlight post-transcriptional gene expression nexus unveils unanticipated SF3B1-dependent vulnerabilities.

Language: Английский

Citations

24
NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation DOI Creative Commons
Xuran Zhang, Ke An, Xin Ge

et al.

Breast Cancer Research, Journal Year: 2024, Volume and Issue: 26(1)

Published: June 6, 2024

Abstract Background RNA m 5 C methylation has been extensively implicated in the occurrence and development of tumors. As main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, precise impact NSUN2-mediated modification on breast cancer (BC) remains unclear. Our study aims to elucidate molecular mechanism underlying how regulates target gene HGH1 (also known as FAM203 ) through modification, thereby promoting BC progression. Additionally, this targets at preliminarily clarifying biological roles BC. Methods Tumor adjacent tissues from patients were collected, was screened sequencing (RNA-seq) single-base resolution (RNA-BisSeq). Methylation immunoprecipitation-qPCR (MeRIP-qPCR) RNA-binding protein (RIP-qPCR) confirmed that molecules YBX1 specifically recognized bound modification. In addition, proteomics, co-immunoprecipitation (co-IP), Ribosome (Ribo-Seq) used explore Results molecule, is abnormally overexpressed increases overall level C. Knocking down can inhibit progression vitro or vivo. Combined RNA-seq RNA-BisSeq analysis identified potential abnormal modifications. We clarified by which expression process involves interactions with protein, collectively impacts mRNA stability synthesis. Furthermore, first reveal binding interaction between translation elongation factor EEF2, providing comprehensive understanding its ability regulate transcript efficiency synthesis cells. Conclusions This clarifies NSUN2-YBX1-m C-HGH1 axis post-transcriptional translation, revealing key suggesting may be new epigenetic biomarker therapeutic for

Language: Английский

Citations

13
RNA editing enzymes: structure, biological functions and applications DOI Creative Commons
Dejiu Zhang,

Lei Zhu,

Yanyan Gao

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 16, 2024

Abstract With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few these can lead to base pair changes, which are called editing. editing is ubiquitous modification in mammalian transcriptomes an important co/posttranscriptional that plays crucial role various cellular processes. There two main types events: adenosine inosine (A-to-I) editing, catalyzed by ADARs on double-stranded or ADATs tRNA, cytosine uridine (C-to-U) APOBECs. This article provides overview structure, function, applications enzymes. We discuss structural characteristics three enzyme families their catalytic mechanisms also explain biological particularly innate immunity, cancer biogenesis, antiviral activity. Additionally, this describes tools for manipulating correct disease-causing mutations, as well potential enzymes field biotechnology therapy.

Language: Английский

Citations

12
Revolutionizing in vivo therapy with CRISPR/Cas genome editing: breakthroughs, opportunities and challenges DOI Creative Commons

Arturo Macarrón Palacios,

Patrick Korus,

Bodo G. C. Wilkens

et al.

Frontiers in Genome Editing, Journal Year: 2024, Volume and Issue: 6

Published: Feb. 1, 2024

Genome editing using the CRISPR/Cas system has revolutionized field of genetic engineering, offering unprecedented opportunities for therapeutic applications in vivo . Despite numerous ongoing clinical trials focusing on ex genome editing, recent studies emphasize promise gene technology. However, it is worth noting that complete attainment inherent capabilities therapy humans yet to be accomplished. Before full realization potential, crucial achieve enhanced specificity selectively targeting defective cells while minimizing harm healthy cells. This review examines emerging studies, CRISPR/Cas-based pre-clinical and innovative approaches a wide range diseases. Furthermore, we cancer-specific sequences target genes associated with tumors, shedding light diverse strategies employed cancer treatment. We highlight various challenges explore their prospective translatability overcome these obstacles.

Language: Английский

Citations

10