Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine
Alternative splicing promotes proteome diversity by using limited number of genes, a key control point of gene expression. Splicing is carried out by large macromolecular machineries, called spliceosome, composed of small RNAs and proteins. Alternative splicing is regulated by splicing regulatory &l...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1381 |
| _version_ | 1797566852453367808 |
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| author | Mohammad Alinoor Rahman Farhana Nasrin Sonali Bhattacharjee Saikat Nandi |
| author_facet | Mohammad Alinoor Rahman Farhana Nasrin Sonali Bhattacharjee Saikat Nandi |
| author_sort | Mohammad Alinoor Rahman |
| collection | DOAJ |
| description | Alternative splicing promotes proteome diversity by using limited number of genes, a key control point of gene expression. Splicing is carried out by large macromolecular machineries, called spliceosome, composed of small RNAs and proteins. Alternative splicing is regulated by splicing regulatory <i>cis</i>-elements in RNA and <i>trans</i>-acting splicing factors that are often tightly regulated in a tissue-specific and developmental stage-specific manner. The biogenesis of ribonucleoprotein (RNP) complexes is strictly regulated to ensure that correct complements of RNA and proteins are coordinated in the right cell at the right time to support physiological functions. Any perturbations that impair formation of functional spliceosomes by disrupting the <i>cis</i>-elements, or by compromising RNA-binding or function of <i>trans</i>-factors can be deleterious to cells and result in pathological consequences. The recent discovery of oncogenic mutations in splicing factors, and growing evidence of the perturbed splicing in multiple types of cancer, underscores RNA processing defects as a critical driver of oncogenesis. These findings have resulted in a growing interest in targeting RNA splicing as a therapeutic approach for cancer treatment. This review summarizes our current understanding of splicing alterations in cancer, recent therapeutic efforts targeting splicing defects in cancer, and future potentials to develop novel cancer therapies. |
| first_indexed | 2024-03-10T19:33:15Z |
| format | Article |
| id | doaj.art-f6b11b67b629486799f640d038ff59f9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:33:15Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f6b11b67b629486799f640d038ff59f92023-11-20T01:59:59ZengMDPI AGCancers2072-66942020-05-01126138110.3390/cancers12061381Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized MedicineMohammad Alinoor Rahman0Farhana Nasrin1Sonali Bhattacharjee2Saikat Nandi3Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USAAlternative splicing promotes proteome diversity by using limited number of genes, a key control point of gene expression. Splicing is carried out by large macromolecular machineries, called spliceosome, composed of small RNAs and proteins. Alternative splicing is regulated by splicing regulatory <i>cis</i>-elements in RNA and <i>trans</i>-acting splicing factors that are often tightly regulated in a tissue-specific and developmental stage-specific manner. The biogenesis of ribonucleoprotein (RNP) complexes is strictly regulated to ensure that correct complements of RNA and proteins are coordinated in the right cell at the right time to support physiological functions. Any perturbations that impair formation of functional spliceosomes by disrupting the <i>cis</i>-elements, or by compromising RNA-binding or function of <i>trans</i>-factors can be deleterious to cells and result in pathological consequences. The recent discovery of oncogenic mutations in splicing factors, and growing evidence of the perturbed splicing in multiple types of cancer, underscores RNA processing defects as a critical driver of oncogenesis. These findings have resulted in a growing interest in targeting RNA splicing as a therapeutic approach for cancer treatment. This review summarizes our current understanding of splicing alterations in cancer, recent therapeutic efforts targeting splicing defects in cancer, and future potentials to develop novel cancer therapies.https://www.mdpi.com/2072-6694/12/6/1381splicingspliceosomecancer therapiesoncogenesisRNA processing |
| spellingShingle | Mohammad Alinoor Rahman Farhana Nasrin Sonali Bhattacharjee Saikat Nandi Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine Cancers splicing spliceosome cancer therapies oncogenesis RNA processing |
| title | Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine |
| title_full | Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine |
| title_fullStr | Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine |
| title_full_unstemmed | Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine |
| title_short | Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine |
| title_sort | hallmarks of splicing defects in cancer clinical applications in the era of personalized medicine |
| topic | splicing spliceosome cancer therapies oncogenesis RNA processing |
| url | https://www.mdpi.com/2072-6694/12/6/1381 |
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