The Physiological Roles of the Exon Junction Complex in Development and Diseases

Asthana, Shravan; Martin, Hannah; Rupkey, Julian; Patel, Shray; Yoon, Joy; Keegan, Abiageal; Mao, Ying

doi:10.3390/cells11071192

Cited by 14 publications

(6 citation statements)

References 169 publications

(239 reference statements)

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“…In these macromolecular-guided processes, correct RNA-protein and protein-protein interactions need to be ensured and meticulous regulation is necessarily required [ 24 ]. In this sense, machineries like the exon-junction complex (EJC) interacts with RNA processing or decays complexes to ensure correct RNA maturation [ 25 ].…”

Section: Rna Biology and Surveillancementioning

confidence: 99%

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities

Blázquez‐Encinas

Moreno-Montilla

García-Vioque

et al. 2022

Rev Endocr Metab Disord

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Neuroendocrine neoplasms (NENs) comprise a highly heterogeneous group of tumors arising from the diffuse neuroendocrine system. NENs mainly originate in gastrointestinal, pancreatic, and pulmonary tissues, and despite being rare, show rising incidence. The molecular mechanisms underlying NEN development are still poorly understood, although recent studies are unveiling their genomic, epigenomic and transcriptomic landscapes. RNA was originally considered as an intermediary between DNA and protein. Today, compelling evidence underscores the regulatory relevance of RNA processing, while new RNA molecules emerge with key functional roles in core cell processes. Indeed, correct functioning of the interrelated complementary processes comprising RNA biology, its processing, transport, and surveillance, is essential to ensure adequate cell homeostasis, and its misfunction is related to cancer at multiple levels. This review is focused on the dysregulation of RNA biology in NENs. In particular, we survey alterations in the splicing process and available information implicating the main RNA species and processes in NENs pathology, including their role as biomarkers, and their functionality and targetability. Understanding how NENs precisely (mis)behave requires a profound knowledge at every layer of their heterogeneity, to help improve NEN management. RNA biology provides a wide spectrum of previously unexplored processes and molecules that open new avenues for NEN detection, classification and treatment. The current molecular biology era is rapidly evolving to facilitate a detailed comprehension of cancer biology and is enabling the arrival of personalized, predictive and precision medicine to rare tumors like NENs. Supplementary Information The online version contains supplementary material available at 10.1007/s11154-022-09771-4.

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Section: Rna Biology and Surveillancementioning

confidence: 99%

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities

Blázquez‐Encinas

Moreno-Montilla

García-Vioque

et al. 2022

Rev Endocr Metab Disord

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“…Certain cell types and tissues show high sensitivity to changes in expression of EJC members [ 58 ]. MAGOH, MAGOHB, and EIF4A3 display high expression levels during early stages of cortex formation [ 36 ] and reduced levels in differentiated neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

et al. 2023

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The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumour development. High MAGOH/MAGOHB expression was observed in 14 tumour types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM.

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“…Certain cell types and tissues show high sensitivity to changes in expression of EJC members (Asthana et al, 2022). MAGOH, MAGOHB, and EIF4A3 display high expression levels during early stages of cortex formation (van de Leemput et al, 2014) and reduced levels in differentiated neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

Barreiro

Guardia

Meliso

et al. 2022

Preprint

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The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumor development. High MAGOH/MAGOHB expression was observed in 14 tumor types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM.

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The Physiological Roles of the Exon Junction Complex in Development and Diseases

Cited by 14 publications

References 169 publications

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities

The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

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