The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer
<p dir="ltr">Alternative splicing allows for the expression of multiple RNA and protein isoforms from one gene, making it a major contributor to transcriptome and proteome diversification in eukaryotes. Advances in next generation sequencing technologies and genome-wide analyses have...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| مؤلفون آخرون: | |
| منشور في: |
2018
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1864513522162991104 |
|---|---|
| author | Ettaib El Marabti (23276158) |
| author2 | Ihab Younis (57824) |
| author2_role | author |
| author_facet | Ettaib El Marabti (23276158) Ihab Younis (57824) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ettaib El Marabti (23276158) Ihab Younis (57824) |
| dc.date.none.fl_str_mv | 2018-09-07T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fmolb.2018.00080 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_Cancer_Spliceome_Reprograming_of_Alternative_Splicing_in_Cancer/31445944 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis splicing cancer spliceome alternative splicing exons introns |
| dc.title.none.fl_str_mv | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Alternative splicing allows for the expression of multiple RNA and protein isoforms from one gene, making it a major contributor to transcriptome and proteome diversification in eukaryotes. Advances in next generation sequencing technologies and genome-wide analyses have recently underscored the fact that the vast majority of multi-exon genes under normal physiology engage in alternative splicing in tissue-specific and developmental-specific manner. On the other hand, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms. These isoforms and their encoded proteins are not insignificant byproducts of the abnormal physiology of cancer cells, but either drivers of cancer progression or small but significant contributors to specific cancer hallmarks. Thus, it is paramount that the pathways that regulate alternative splicing in cancer, including the splicing factors that bind to pre-mRNAs and modulate spliceosome recruitment. In this review, we present a few distinct cases of alternative splicing in cancer, with an emphasis on their regulation as well as their contribution to cancer cell phenotype. Several categories of splicing aberrations are highlighted, including alterations in cancer-related genes that directly affect their pre-mRNA splicing, mutations in genes encoding splicing factors or core spliceosomal subunits, and the seemingly mutation-free disruptions in the balance of the expression of RNA-binding proteins, including components of both the major (U2-dependent) and minor (U12-dependent) spliceosomes. Given that the latter two classes cause global alterations in splicing that affect a wide range of genes, it remains a challenge to identify the ones that contribute to cancer progression. These challenges necessitate a systematic approach to decipher these aberrations and their impact on cancer. Ultimately, a sufficient understanding of splicing deregulation in cancer is predicted to pave the way for novel and innovative RNA-based therapies.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Frontiers in Molecular Biosciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fmolb.2018.00080" target="_blank">https://dx.doi.org/10.3389/fmolb.2018.00080</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_86f525097c3609fc59bdff0139a630ea |
| identifier_str_mv | 10.3389/fmolb.2018.00080 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/31445944 |
| publishDate | 2018 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The Cancer Spliceome: Reprograming of Alternative Splicing in CancerEttaib El Marabti (23276158)Ihab Younis (57824)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesOncology and carcinogenesissplicingcancer spliceomealternative splicingexonsintrons<p dir="ltr">Alternative splicing allows for the expression of multiple RNA and protein isoforms from one gene, making it a major contributor to transcriptome and proteome diversification in eukaryotes. Advances in next generation sequencing technologies and genome-wide analyses have recently underscored the fact that the vast majority of multi-exon genes under normal physiology engage in alternative splicing in tissue-specific and developmental-specific manner. On the other hand, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms. These isoforms and their encoded proteins are not insignificant byproducts of the abnormal physiology of cancer cells, but either drivers of cancer progression or small but significant contributors to specific cancer hallmarks. Thus, it is paramount that the pathways that regulate alternative splicing in cancer, including the splicing factors that bind to pre-mRNAs and modulate spliceosome recruitment. In this review, we present a few distinct cases of alternative splicing in cancer, with an emphasis on their regulation as well as their contribution to cancer cell phenotype. Several categories of splicing aberrations are highlighted, including alterations in cancer-related genes that directly affect their pre-mRNA splicing, mutations in genes encoding splicing factors or core spliceosomal subunits, and the seemingly mutation-free disruptions in the balance of the expression of RNA-binding proteins, including components of both the major (U2-dependent) and minor (U12-dependent) spliceosomes. Given that the latter two classes cause global alterations in splicing that affect a wide range of genes, it remains a challenge to identify the ones that contribute to cancer progression. These challenges necessitate a systematic approach to decipher these aberrations and their impact on cancer. Ultimately, a sufficient understanding of splicing deregulation in cancer is predicted to pave the way for novel and innovative RNA-based therapies.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Frontiers in Molecular Biosciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fmolb.2018.00080" target="_blank">https://dx.doi.org/10.3389/fmolb.2018.00080</a></p>2018-09-07T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fmolb.2018.00080https://figshare.com/articles/journal_contribution/The_Cancer_Spliceome_Reprograming_of_Alternative_Splicing_in_Cancer/31445944CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/314459442018-09-07T03:00:00Z |
| spellingShingle | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer Ettaib El Marabti (23276158) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis splicing cancer spliceome alternative splicing exons introns |
| status_str | publishedVersion |
| title | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| title_full | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| title_fullStr | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| title_full_unstemmed | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| title_short | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| title_sort | The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis splicing cancer spliceome alternative splicing exons introns |