Regulating Divergent Transcriptomes through mRNA Splicing and Its Modulation Using Various Small Compounds
Human transcriptomes are more divergent than genes and contribute to the sophistication of life. This divergence is derived from various isoforms arising from alternative splicing. In addition, alternative splicing regulated by spliceosomal factors and RNA structures, such as the RNA G-quadruplex, i...
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| Veröffentlicht in: | International journal of molecular sciences 2020-03, Vol.21 (6), p.2026 |
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| creator | Fujita, Ken-Ichi Ishizuka, Takaki Mitsukawa, Mizuki Kurata, Masashi Masuda, Seiji |
| description | Human transcriptomes are more divergent than genes and contribute to the sophistication of life. This divergence is derived from various isoforms arising from alternative splicing. In addition, alternative splicing regulated by spliceosomal factors and RNA structures, such as the RNA G-quadruplex, is important not only for isoform diversity but also for regulating gene expression. Therefore, abnormal splicing leads to serious diseases such as cancer and neurodegenerative disorders. In the first part of this review, we describe the regulation of divergent transcriptomes using alternative mRNA splicing. In the second part, we present the relationship between the disruption of splicing and diseases. Recently, various compounds with splicing inhibitor activity were established. These splicing inhibitors are recognized as a biological tool to investigate the molecular mechanism of splicing and as a potential therapeutic agent for cancer treatment. Food-derived compounds with similar functions were found and are expected to exhibit anticancer effects. In the final part, we describe the compounds that modulate the messenger RNA (mRNA) splicing process and their availability for basic research and future clinical potential. |
| doi_str_mv | 10.3390/ijms21062026 |
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This divergence is derived from various isoforms arising from alternative splicing. In addition, alternative splicing regulated by spliceosomal factors and RNA structures, such as the RNA G-quadruplex, is important not only for isoform diversity but also for regulating gene expression. Therefore, abnormal splicing leads to serious diseases such as cancer and neurodegenerative disorders. In the first part of this review, we describe the regulation of divergent transcriptomes using alternative mRNA splicing. In the second part, we present the relationship between the disruption of splicing and diseases. Recently, various compounds with splicing inhibitor activity were established. These splicing inhibitors are recognized as a biological tool to investigate the molecular mechanism of splicing and as a potential therapeutic agent for cancer treatment. Food-derived compounds with similar functions were found and are expected to exhibit anticancer effects. In the final part, we describe the compounds that modulate the messenger RNA (mRNA) splicing process and their availability for basic research and future clinical potential.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21062026</identifier><identifier>PMID: 32188117</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alternative Splicing ; Cell cycle ; Chemical compounds ; Cytoplasm ; Disruption ; Exports ; Gene expression ; Gene Expression Regulation ; Humans ; Isoforms ; Localization ; Mammals ; Mutation ; Neoplasms - genetics ; Neoplasms - metabolism ; Neurodegenerative Diseases - metabolism ; Pharmacology ; Protein expression ; Protein Isoforms ; Proteins ; Review ; RNA Splicing - physiology ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Spliceosomes - metabolism ; Splicing ; Transcriptome</subject><ispartof>International journal of molecular sciences, 2020-03, Vol.21 (6), p.2026</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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Ishizuka, Takaki ; Mitsukawa, Mizuki ; Kurata, Masashi ; Masuda, Seiji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-50aa79cbeccbc5ccb16a215c35f78d6f43bc47431b3dca8cfb71de552e1b2873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alternative Splicing</topic><topic>Cell cycle</topic><topic>Chemical compounds</topic><topic>Cytoplasm</topic><topic>Disruption</topic><topic>Exports</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Isoforms</topic><topic>Localization</topic><topic>Mammals</topic><topic>Mutation</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neurodegenerative Diseases - metabolism</topic><topic>Pharmacology</topic><topic>Protein expression</topic><topic>Protein Isoforms</topic><topic>Proteins</topic><topic>Review</topic><topic>RNA Splicing - physiology</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Spliceosomes - metabolism</topic><topic>Splicing</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujita, Ken-Ichi</creatorcontrib><creatorcontrib>Ishizuka, Takaki</creatorcontrib><creatorcontrib>Mitsukawa, Mizuki</creatorcontrib><creatorcontrib>Kurata, Masashi</creatorcontrib><creatorcontrib>Masuda, Seiji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujita, Ken-Ichi</au><au>Ishizuka, Takaki</au><au>Mitsukawa, Mizuki</au><au>Kurata, Masashi</au><au>Masuda, Seiji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulating Divergent Transcriptomes through mRNA Splicing and Its Modulation Using Various Small Compounds</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-03-16</date><risdate>2020</risdate><volume>21</volume><issue>6</issue><spage>2026</spage><pages>2026-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Human transcriptomes are more divergent than genes and contribute to the sophistication of life. 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| subjects | Alternative Splicing Cell cycle Chemical compounds Cytoplasm Disruption Exports Gene expression Gene Expression Regulation Humans Isoforms Localization Mammals Mutation Neoplasms - genetics Neoplasms - metabolism Neurodegenerative Diseases - metabolism Pharmacology Protein expression Protein Isoforms Proteins Review RNA Splicing - physiology RNA, Messenger - genetics RNA, Messenger - metabolism Spliceosomes - metabolism Splicing Transcriptome |
| title | Regulating Divergent Transcriptomes through mRNA Splicing and Its Modulation Using Various Small Compounds |
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