Ribosome biogenesis in disease: new players and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 9, 2023

Abstract The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis the process generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, transformation. mTORC1, Myc, noncoding RNA signaling pathways are primary mediators work jointly with polymerases proteins to control protein synthesis. Activation of mTORC1 required for normal fetal growth development tissue regeneration after birth. Myc implicated cancer by enhancing Pol II activity, leading uncontrolled growth. deregulation RNAs such as microRNAs, long RNAs, circular involved developing blood, neurodegenerative diseases, atherosclerosis. We review similarities differences between eukaryotic bacterial molecular mechanism ribosome-targeting antibiotics resistance. also most recent findings dysfunction COVID-19 other conditions discuss consequences frameshifting, ribosome-stalling, ribosome-collision. summarize various diseases. Furthermore, we current clinical trials, prospective vaccines COVID-19, therapies targeting cancer, cardiovascular disease, aging, disease.

Language: Английский

---

Role of main RNA modifications in cancer: N6-methyladenosine, 5-methylcytosine, and pseudouridine

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 28, 2022

Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in genetic material without any nucleic acid sequence results phenotypic changes. modifications regulate many biological processes, such as growth, aging, various diseases, including cancer. With advancement next-generation sequencing technology, role RNA cancer progression has become increasingly prominent a hot spot scientific research. This review studied several common modifications, N6-methyladenosine, 5-methylcytosine, pseudouridine. The deposition roles these coding noncoding RNAs are summarized detail. Based on background, this expression, function, underlying molecular mechanism their regulators further discussed some existing small-molecule inhibitors. More in-depth studies needed broaden understanding epigenetics diagnosis, treatment, prognosis.

Language: Английский

---

Epitranscriptome: Review of Top 25 Most-Studied RNA Modifications

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13851 - 13851

Published: Nov. 10, 2022

The alphabet of building blocks for RNA molecules is much larger than the standard four nucleotides. diversity achieved by post-transcriptional biochemical modification these nucleotides into distinct chemical entities that are structurally and functionally different from their unmodified counterparts. Some modifications constituent critical functions, while others serve as dynamic markings to regulate fate specific molecules. Together, form epitranscriptome, an essential layer cellular biochemistry. As time writing this review, more 300 all three life domains have been identified. However, only a few most well-established included in reviews on topic. To provide complete overview current state research we analyzed extent available information known modifications. We selected 25 describe detail. Summarizing our findings, status identify further developments field.

Language: Английский

---

Alterations of ribosomal RNA pseudouridylation in human breast cancer

NAR Cancer, Journal Year: 2023, Volume and Issue: 5(2)

Published: March 11, 2023

Abstract RNA modifications are key regulatory factors for several biological and pathological processes. They abundantly represented on ribosomal (rRNA), where they contribute to regulate function in mRNA translation. Altered modification pathways have been linked tumorigenesis as well other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern rRNA breast cancer samples exploiting RBS-Seq technique involving bisulfite treatment coupled with a new NGS approach. We found wide variability among patients at different sites. The most dysregulated positions tumors turned out be hypermodified respect reference RNA. As 2′O-methylation level of modification, detected variable stable pseudouridine sites, sites being evolutionary conserved. also observed that levels specific related some clinical bio-pathological tumor features able distinguish patient clusters. This is first example contribution newly available high-throughput approaches site detection can provide understanding intrinsic changes occurring tumors.

Language: Английский

---

Control of protein synthesis through mRNA pseudouridylation by dyskerin

Science Advances, Journal Year: 2023, Volume and Issue: 9(30)

Published: July 28, 2023

Posttranscriptional modifications of mRNA have emerged as regulators gene expression. Although pseudouridylation is the most abundant, its biological role remains poorly understood. Here, we demonstrate that pseudouridine synthase dyskerin associates with RNA polymerase II, binds to thousands mRNAs, and responsible for their pseudouridylation, an action occurs in chromatin does not appear require a guide full complementarity. In cells lacking dyskerin, reduced, while at same time, de novo protein synthesis enhanced, indicating this modification interferes translation. Accordingly, mRNAs fewer pseudouridines due knockdown are translated more efficiently. Moreover, severely reduced patients dyskeratosis congenita caused by inherited mutations encoding (i.e., DKC1). Our findings modulates translatability, important implications both normal development disease.

Language: Английский

---

The mTOR Signaling Pathway Interacts with the ER Stress Response and the Unfolded Protein Response in Cancer

Cancer Research, Journal Year: 2023, Volume and Issue: 83(15), P. 2450 - 2460

Published: May 17, 2023

The mTOR complex 1 (mTORC1) coordinates several important environmental and intracellular cues to control a variety of biological processes, such as cell growth, survival, autophagy, metabolism, in response energy levels, growth signals, nutrients. endoplasmic reticulum (ER) is crucial organelle that essential for numerous cellular functions, including the synthesis, folding, modification newly synthesized proteins, stress responsiveness, maintainence homeostasis. mTOR-mediated upregulation protein synthesis induces accumulation misfolded or unfolded proteins ER lumen, which stress, leading activation (UPR) pathway. Reciprocally, regulates PI3K/AKT/mTOR signaling Therefore, under pathologic conditions, cross-talk between UPR pathways during can critically affect cancer fate may be involved pathogenesis therapeutic outcome cancer. Here, we discuss accumulating evidence showing mechanism action, interconnections, molecular links tumorigenesis highlights potential implications cancers.

Language: Английский

---

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(4)

Published: April 1, 2024

Abstract RNA methylation is widespread in nature. Abnormal expression of proteins associated with strongly a number human diseases including cancer. Increasing evidence suggests that targeting holds promise for cancer treatment. This review specifically describes several common modifications, such as the relatively well‐studied N6‐methyladenosine, well 5‐methylcytosine and pseudouridine (Ψ). The regulatory factors involved these modifications their roles are also comprehensively discussed. We summarise diverse functions across different types RNAs. Furthermore, we elucidate structural characteristics along development specific inhibitors them. Additionally, recent advancements small molecule presented to underscore immense potential clinical significance enhancing therapeutic efficacy against Key Points In this paper, important related systematically summarised. Several modification were progression, relationships cell migration, invasion, drug resistance immune environment regulators have been proposed studies summarised detail, which great treatment future.

Language: Английский

---

Crossing boundaries of light microscopy resolution discerns novel assemblies in the nucleolus

Histochemistry and Cell Biology, Journal Year: 2024, Volume and Issue: 162(1-2), P. 161 - 183

Published: May 17, 2024

Language: Английский

---

RNA modifications in cancer

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Language: Английский

---

Managing Telomerase and Telomere Dysfunction in Acral Melanoma

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107700 - 107700

Published: March 1, 2025

Acral Lentiginous Melanoma is a rare and aggressive subtype of melanoma that commonly affects the palms, soles, nail beds. It more prevalent in individuals with darker skin tones, including Asian, African, Hispanic populations. Unlike cutaneous melanomas, acral not associated UV exposure has distinct genetic molecular profile, underscoring need for tailored research treatment strategies. Standard treatments, such as surgery, chemotherapy, immunotherapy, targeted therapies, have shown limited success this subtype, highlighting urgency developing effective interventions. Telomerase an enzyme extends telomeres key target which exhibits' high telomerase activity, driven by mutations reverse transcriptase TERT promoter, contributes to uncontrolled tumor cell proliferation, cancer immortality, resistance conventional therapies. Therefore, targeting presents promising therapeutic avenue patients who do respond well current treatments. Several approaches deregulation been developed, their potential management discussed review. Specifically, promise telomerase-targeted therapies emphasized explores how these strategies could improve outcomes challenging cancer. By focusing on role tumorigenesis resistance, hold foundational component melanoma, complementing existing approaches.

Language: Английский

---