We skip to work: alternative splicing in normal and malignant myelopoiesis

Wong, Alex C. H.; Rasko, John E.J.; Wong, Justin

doi:10.1038/s41375-018-0021-4

Cited by 33 publications

(32 citation statements)

References 114 publications

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“…Interestingly, even if aberrant alternative splicing plays a relevant role in AML [57] and m 6 A modification has an established role in regulating alternative splicing, mRNA translation has been identified as the main regulatory step deregulated by m 6 A in AML [51,52,53]. Therein, the YTHDF1 reader should mediate most of the observed phenotype in AML.…”

Section: M6a Roles In Aml (Acute Myeloid Leukaemia) and Normal Haementioning

confidence: 99%

N6-Methyladenosine Role in Acute Myeloid Leukaemia

Ianniello

Fatica

2018

IJMS

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We 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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Section: M6a Roles In Aml (Acute Myeloid Leukaemia) and Normal Haementioning

confidence: 99%

N6-Methyladenosine Role in Acute Myeloid Leukaemia

Ianniello

Fatica

2018

IJMS

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“…Changes in expression levels and specific binding of the hnRNP A/B protein affect this developmental switch 15 . Since then, alternative splicing has emerged as a more widespread phenomenon 16– 18 . The muscleblind-like protein 1 (MBNL1) is a sequence-specific splicing factor that undergoes extensive alternative splicing during differentiation 17 .…”

Section: Splicing Regulation In Normal Erythropoiesismentioning

confidence: 99%

Blood Relatives: Splicing Mechanisms underlying Erythropoiesis in Health and Disease

Reimer

Neugebauer

2018

F1000Res

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During erythropoiesis, hematopoietic stem and progenitor cells transition to erythroblasts en route to terminal differentiation into enucleated red blood cells. Transcriptome-wide changes underlie distinct morphological and functional characteristics at each cell division during this process. Many studies of gene expression have historically been carried out in erythroblasts, and the biogenesis of β-globin mRNA—the most highly expressed transcript in erythroblasts—was the focus of many seminal studies on the mechanisms of pre-mRNA splicing. We now understand that pre-mRNA splicing plays an important role in shaping the transcriptome of developing erythroblasts. Recent advances have provided insight into the role of alternative splicing and intron retention as important regulatory mechanisms of erythropoiesis. However, dysregulation of splicing during erythropoiesis is also a cause of several hematological diseases, including β-thalassemia and myelodysplastic syndromes. With a growing understanding of the role that splicing plays in these diseases, we are well poised to develop gene-editing treatments. In this review, we focus on changes in the developing erythroblast transcriptome caused by alternative splicing, the molecular basis of splicing-related blood diseases, and therapeutic advances in disease treatment using CRISPR/Cas9 gene editing.

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“…Interestingly, even if aberrant alternative splicing plays a relevant role in AML [57] and m 6 A modification has an established role in regulating alternative splicing, mRNA translation has been identified as the main regulatory step deregulated by m 6 A in AML [51][52][53]. Therein, the YTHDF1 reader should mediate most of the observed phenotype in AML.…”

Section: A Roles In Aml and Normal Haematopoiesismentioning

confidence: 99%

N6-Methyladenosine Role in Cancer: Learning from AML

Ianniello¹,

Fatica²

2018

Preprint

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We are currently assisting at the explosion of the 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 AML that, among first, has indicated how alteration in m6A modification can disrupt normal cellular differentiation and lead to cancer.

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We skip to work: alternative splicing in normal and malignant myelopoiesis

Cited by 33 publications

References 114 publications

N6-Methyladenosine Role in Acute Myeloid Leukaemia

N6-Methyladenosine Role in Acute Myeloid Leukaemia

Blood Relatives: Splicing Mechanisms underlying Erythropoiesis in Health and Disease

N6-Methyladenosine Role in Cancer: Learning from AML

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