Linking Endoplasmic Reticular Stress and Alternative Splicing
RNA splicing patterns in antibody-secreting cells are shaped by endoplasmic reticulum stress, (eleven-nineteen lysine-rich leukemia gene 2) induction, and changes in the levels of s. Endoplasmic reticulum stress induces the unfolded protein response comprising a highly conserved set of genes crucial...
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| Veröffentlicht in: | International journal of molecular sciences 2018-12, Vol.19 (12), p.3919 |
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| creator | Carew, Nolan T Nelson, Ashley M Liang, Zhitao Smith, Sage M Milcarek, Christine |
| description | RNA splicing patterns in antibody-secreting cells are shaped by endoplasmic reticulum stress,
(eleven-nineteen lysine-rich leukemia gene 2) induction, and changes in the levels of
s. Endoplasmic reticulum stress induces the unfolded protein response comprising a highly conserved set of genes crucial for cell survival; among these is Ire1, whose auto-phosphorylation drives it to acquire a regulated mRNA decay activity. The mRNA-modifying function of phosphorylated Ire1 non-canonically splices Xbp1 mRNA and yet degrades other cellular mRNAs with related motifs. Naïve splenic B cells will activate Ire1 phosphorylation early on after lipopolysaccharide (LPS) stimulation, within 18 h; large-scale changes in mRNA content and splicing patterns result. Inhibition of the mRNA-degradation function of Ire1 is correlated with further differences in the splicing patterns and a reduction in the mRNA factors for snRNA transcription. Some of the >4000 splicing changes seen at 18 h after LPS stimulation persist into the late stages of antibody secretion, up to 72 h. Meanwhile some early splicing changes are supplanted by new splicing changes introduced by the up-regulation of ELL2, a transcription elongation factor. ELL2 is necessary for immunoglobulin secretion and does this by changing mRNA processing patterns of immunoglobulin heavy chain and >5000 other genes. |
| doi_str_mv | 10.3390/ijms19123919 |
| format | Article |
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s. Endoplasmic reticulum stress induces the unfolded protein response comprising a highly conserved set of genes crucial for cell survival; among these is Ire1, whose auto-phosphorylation drives it to acquire a regulated mRNA decay activity. The mRNA-modifying function of phosphorylated Ire1 non-canonically splices Xbp1 mRNA and yet degrades other cellular mRNAs with related motifs. Naïve splenic B cells will activate Ire1 phosphorylation early on after lipopolysaccharide (LPS) stimulation, within 18 h; large-scale changes in mRNA content and splicing patterns result. Inhibition of the mRNA-degradation function of Ire1 is correlated with further differences in the splicing patterns and a reduction in the mRNA factors for snRNA transcription. Some of the >4000 splicing changes seen at 18 h after LPS stimulation persist into the late stages of antibody secretion, up to 72 h. Meanwhile some early splicing changes are supplanted by new splicing changes introduced by the up-regulation of ELL2, a transcription elongation factor. ELL2 is necessary for immunoglobulin secretion and does this by changing mRNA processing patterns of immunoglobulin heavy chain and >5000 other genes.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms19123919</identifier><identifier>PMID: 30544499</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alternative splicing ; Alternative Splicing - genetics ; Alternative Splicing - physiology ; Animals ; Antibodies ; Apoptosis ; B-Lymphocytes - metabolism ; Cytoplasm ; Elongation ; Endoplasmic reticulum ; Endoplasmic Reticulum Stress - genetics ; Endoplasmic Reticulum Stress - physiology ; Enzymes ; Gene regulation ; Genes ; Humans ; Immunoglobulins ; Insects ; Kinases ; Leukemia ; Lipopolysaccharides ; Liver ; Lymphocytes B ; Lysine ; Metabolism ; mRNA processing ; mRNA turnover ; Phosphorylation ; Protein folding ; Protein synthesis ; Review ; RNA Splicing - genetics ; RNA, Messenger - metabolism ; snRNA ; Spleen ; Splicing ; Stimulation ; Transcription factors ; Unfolded Protein Response - genetics ; Unfolded Protein Response - physiology</subject><ispartof>International journal of molecular sciences, 2018-12, Vol.19 (12), p.3919</ispartof><rights>2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-ea262db60ff520b32701783ef7a7b8b82b38b41f4a5d853588b57ee98bb6a6343</citedby><cites>FETCH-LOGICAL-c478t-ea262db60ff520b32701783ef7a7b8b82b38b41f4a5d853588b57ee98bb6a6343</cites><orcidid>0000-0002-6995-6823</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321306/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321306/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30544499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carew, Nolan T</creatorcontrib><creatorcontrib>Nelson, Ashley M</creatorcontrib><creatorcontrib>Liang, Zhitao</creatorcontrib><creatorcontrib>Smith, Sage M</creatorcontrib><creatorcontrib>Milcarek, Christine</creatorcontrib><title>Linking Endoplasmic Reticular Stress and Alternative Splicing</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>RNA splicing patterns in antibody-secreting cells are shaped by endoplasmic reticulum stress,
(eleven-nineteen lysine-rich leukemia gene 2) induction, and changes in the levels of
s. Endoplasmic reticulum stress induces the unfolded protein response comprising a highly conserved set of genes crucial for cell survival; among these is Ire1, whose auto-phosphorylation drives it to acquire a regulated mRNA decay activity. The mRNA-modifying function of phosphorylated Ire1 non-canonically splices Xbp1 mRNA and yet degrades other cellular mRNAs with related motifs. Naïve splenic B cells will activate Ire1 phosphorylation early on after lipopolysaccharide (LPS) stimulation, within 18 h; large-scale changes in mRNA content and splicing patterns result. Inhibition of the mRNA-degradation function of Ire1 is correlated with further differences in the splicing patterns and a reduction in the mRNA factors for snRNA transcription. Some of the >4000 splicing changes seen at 18 h after LPS stimulation persist into the late stages of antibody secretion, up to 72 h. Meanwhile some early splicing changes are supplanted by new splicing changes introduced by the up-regulation of ELL2, a transcription elongation factor. ELL2 is necessary for immunoglobulin secretion and does this by changing mRNA processing patterns of immunoglobulin heavy chain and >5000 other genes.</description><subject>Alternative splicing</subject><subject>Alternative Splicing - genetics</subject><subject>Alternative Splicing - physiology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>B-Lymphocytes - metabolism</subject><subject>Cytoplasm</subject><subject>Elongation</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum Stress - genetics</subject><subject>Endoplasmic Reticulum Stress - physiology</subject><subject>Enzymes</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Insects</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>Lymphocytes B</subject><subject>Lysine</subject><subject>Metabolism</subject><subject>mRNA processing</subject><subject>mRNA turnover</subject><subject>Phosphorylation</subject><subject>Protein folding</subject><subject>Protein synthesis</subject><subject>Review</subject><subject>RNA Splicing - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>snRNA</subject><subject>Spleen</subject><subject>Splicing</subject><subject>Stimulation</subject><subject>Transcription factors</subject><subject>Unfolded Protein Response - genetics</subject><subject>Unfolded Protein Response - physiology</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtLAzEUhYMotj52rmXAjQtH85xkFgql1AcUBKvrkMxkampmpiYzBf-9kdZSXd0L97uHczgAnCF4TUgOb-yiDihHmOQo3wNDRDFOIcz4_s4-AEchLCDEBLP8EAwIZJTSPB-C26ltPmwzTyZN2S6dCrUtkhfT2aJ3yiezzpsQEtWUych1xjeqsyuTzJbOFvHrBBxUygVzupnH4O1-8jp-TKfPD0_j0TQtKBddahTOcKkzWFUMQ00wh4gLYiquuBZaYE2EpqiiipWCESaEZtyYXGidqYxQcgzu1rrLXtemLEzTeeXk0tta-S_ZKiv_Xhr7LuftSmYEIwKzKHC5EfDtZ29CJ2sbCuOcakzbB4kR4xnDgsOIXvxDF20fg7tIMYGjP0R4pK7WVOHbELyptmYQlD-9yN1eIn6-G2AL_xZBvgFyO4j5</recordid><startdate>20181207</startdate><enddate>20181207</enddate><creator>Carew, Nolan T</creator><creator>Nelson, Ashley M</creator><creator>Liang, Zhitao</creator><creator>Smith, Sage M</creator><creator>Milcarek, Christine</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6995-6823</orcidid></search><sort><creationdate>20181207</creationdate><title>Linking Endoplasmic Reticular Stress and Alternative Splicing</title><author>Carew, Nolan T ; 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(eleven-nineteen lysine-rich leukemia gene 2) induction, and changes in the levels of
s. Endoplasmic reticulum stress induces the unfolded protein response comprising a highly conserved set of genes crucial for cell survival; among these is Ire1, whose auto-phosphorylation drives it to acquire a regulated mRNA decay activity. The mRNA-modifying function of phosphorylated Ire1 non-canonically splices Xbp1 mRNA and yet degrades other cellular mRNAs with related motifs. Naïve splenic B cells will activate Ire1 phosphorylation early on after lipopolysaccharide (LPS) stimulation, within 18 h; large-scale changes in mRNA content and splicing patterns result. Inhibition of the mRNA-degradation function of Ire1 is correlated with further differences in the splicing patterns and a reduction in the mRNA factors for snRNA transcription. Some of the >4000 splicing changes seen at 18 h after LPS stimulation persist into the late stages of antibody secretion, up to 72 h. Meanwhile some early splicing changes are supplanted by new splicing changes introduced by the up-regulation of ELL2, a transcription elongation factor. ELL2 is necessary for immunoglobulin secretion and does this by changing mRNA processing patterns of immunoglobulin heavy chain and >5000 other genes.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30544499</pmid><doi>10.3390/ijms19123919</doi><orcidid>https://orcid.org/0000-0002-6995-6823</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Alternative splicing Alternative Splicing - genetics Alternative Splicing - physiology Animals Antibodies Apoptosis B-Lymphocytes - metabolism Cytoplasm Elongation Endoplasmic reticulum Endoplasmic Reticulum Stress - genetics Endoplasmic Reticulum Stress - physiology Enzymes Gene regulation Genes Humans Immunoglobulins Insects Kinases Leukemia Lipopolysaccharides Liver Lymphocytes B Lysine Metabolism mRNA processing mRNA turnover Phosphorylation Protein folding Protein synthesis Review RNA Splicing - genetics RNA, Messenger - metabolism snRNA Spleen Splicing Stimulation Transcription factors Unfolded Protein Response - genetics Unfolded Protein Response - physiology |
| title | Linking Endoplasmic Reticular Stress and Alternative Splicing |
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