1,721,041 research outputs found
Noncoding RNAs in Acute Myeloid Leukemia: From Key Regulators to Clinical Players
No full textRecent analyses have shown that human cells transcribe almost their entire genomes, implying the existence of a huge mass of ncRNAs. At the present, microRNAs are the most investigated regulative non-coding RNAs. Several studies have demonstrated that microRNAs play a crucial role in hematopoietic differentiation and hematological malignancies, including acute myeloid leukemia (AML). Aberrant expression of microRNAs has been associated with specific genetic abnormalities and clinical outcome of patients with AML. In addition, since microRNAs can function as either oncogenes or tumor suppressor genes, the potential of using these molecules as therapeutic targets opens up new opportunities in the future of AML therapy. The recent demonstration that other regulatory ncRNAs, in addition to microRNAs, are involved in hematopoietic cell differentiation and diseases, suggests that they may also have a biological relevance in AML. This paper will describe the role of ncRNAs in AML and discuss the expectations for the use of ncRNAs in diagnosis, prognosis, and therapy of AML
Interplay between N6-methyladenosine (m6A) and non-coding RNAs in cell development and cancer
Full text linkRNA chemical modifications in coding and non-coding RNAs have been known for decades. They are generally installed by specific enzymes and, in some cases, can be read and erased by other specific proteins. The impact of RNA chemical modifications on gene expression regulation and the reversible nature of some of these modifications led to the birth of the word epitranscriptomics, in analogy with the changes that occur on DNA and histones. Among more than 100 different modifications identified so far, most of the epitranscriptomics studies focused on the N-6-methyladenosine (m(6)A), which is the more abundant internal modification in protein coding RNAs. m(6)A can control several pathways of gene expression, including spicing, export, stability, and translation. In this review, we describe the interplay between m(6)A and non-coding RNAs, in particular microRNAs and lncRNAs, with examples of its role in gene expression regulation. Finally, we discuss its relevance in cell development and disease
Role of microRNAs in hematological malignancies. (2009)
No full textmicroRNAs (miRNAs) are short noncoding RNAs that function as post-transcriptional negative regulators of gene expression. They have been shown to be involved in the control of cell proliferation and differentiation, as well as acting as oncogenes or tumor-suppressor genes, suggesting their involvement in cancer development and progression. Expression profiles of human miRNAs have shown that many of them are aberrantly expressed in hematological malignancies. Therefore, miRNA profiling may be useful to distinguish between normal and tumor cells, and to create signatures for a variety of leukemia subtypes. Here, we review recent evidence for the involvement of miRNAs in the pathogenesis of different hematopoietic malignancies and their potential applications in diagnosis, prognosis and therapy of human leukemia
Insights into the structure and function of a guide RNP
No full textMany different RNA species undergo nucleotide modifications at sites identified by guide small nucleolar ribonucleoprotein (snoRNP) particles. The co-crystal structure of two snoRNP proteins gives valuable clues into the workings of this system
Yeast snoRNA accumulation relies on a cleavage-dependent/polyadenylation-independent 3’ processing apparatus
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Regulation of ribosome function by RNA modifications in hematopoietic development and leukemia: it is not only a matter of m6A
Full text linkGrowth and maturation of hematopoietic stem cells (HSCs) are largely controlled at both transcriptional and post-transcriptional levels. In particular, hematopoietic development requires a tight control of protein synthesis. Furthermore, translational deregulation strongly contributes to hematopoietic malignancies. Researchers have recently identified a new layer of gene expression regulation that consists of chemical modification of RNA species, which led to the birth of the epitranscriptomics field. RNA modifications provide an additional level of control in hematopoietic development by acting as post-transcriptional regulators of lineage-specific genetic programs. Other reviews have already described the important role of the N6-methylation of adenosine (m6A) within mRNA species in regulating hematopoietic differentiation and diseases. The aim of this review is to summarize the current status of the role of RNA modifications in the regulation of ribosome function, beyond m6A. In particular, we discuss the importance of RNA modifications in tRNA and rRNA molecules. By balancing translational rate and fidelity, they play an important role in regulating normal and malignant hematopoietic development
N6-methyladenosine (m6A) RNA modification in chronic myeloid leukemia: unveiling a novel therapeutic target
Full text linkN6-methyladenosine (m6A), the most prevalent internal mRNA modification, plays a critical role in physiological processes by regulating gene expression through modulation of mRNA metabolism at multiple stages. In recent years, m6A has garnered significant attention for a deeper understanding of the initiation, progression, and drug resistance of various cancers, including hematological malignancies. Dysregulation of m6A has been implicated in both cancer promotion and suppression. m6A methylation is a complex regulatory process involving methyltransferases (writers), demethylases (erasers), and proteins that recognize specific m6A modifications (readers). This intricate interplay presents challenges for precisely modulating m6A levels, either globally or at specific sites. This review specifically focuses on the role of m6A in chronic myeloid leukemia (CML), a blood cancer characterized by the BCR-ABL1 fusion. We emphasize its impact on leukemia cell survival and drug resistance mechanisms. Notably, inhibitors targeting m6A regulators show promise in preclinical models, suggesting a potential therapeutic avenue for CML. Integrating our understanding of m6A biology with current treatment strategies may lead to more effective therapies, especially for patients with advanced-stage or resistant CML
N6-Methyladenosine Role in Acute Myeloid Leukaemia
Full text linkWe are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m6A), in particular, has attracted the interest of researchers all around the world. m6A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation. m6A is installed by "writers", removed by "erasers", and recognized by "readers"; thus, it can be compared to the reversible and dynamic epigenetic modifications in histones and DNA. Given its fundamental role in determining the way mRNAs are expressed, it comes as no surprise that alterations to m6A modifications have a deep impact in cell differentiation, normal development and human diseases. Here, we review the proteins involved in m6A modification in mammals, m6A role in gene expression and its contribution to cancer development. In particular, we will focus on acute myeloid leukaemia (AML), which provides an initial indication of how alteration in m6A modification can disrupt normal cellular differentiation and lead to cancer
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