Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations
We report that stress axis—regulated exon (STREX)-containing calcium-activated big potassium (BKCa) channel splice variant expression and physiology are regulated in part by cytoplasmic splicing and intron retention. NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples fo...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2010-12, Vol.107 (49), p.21152-21157 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Bell, Thomas J. Miyashiro, Kevin Y. Sul, Jai-Yoon Buckley, Peter T. Lee, Miler T. McCullough, Ron Jochems, Jeanine Kim, Junhyong Cantor, Charles R. Parsons, Thomas D. Eberwine, James H. |
| description | We report that stress axis—regulated exon (STREX)-containing calcium-activated big potassium (BKCa) channel splice variant expression and physiology are regulated in part by cytoplasmic splicing and intron retention. NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons. |
| doi_str_mv | 10.1073/pnas.1015264107 |
| format | Article |
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NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1015264107</identifier><identifier>PMID: 21078998</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Action potentials ; Alternative splicing ; Alternative Splicing - genetics ; Animals ; Biological Sciences ; Calcium ; Cells ; Data processing ; Dendrites ; Deoxyribonucleic acid ; DNA ; Exons ; Gene expression ; Hippocampus ; Hippocampus - cytology ; Immunocytochemistry ; Introns ; Introns - genetics ; Large-Conductance Calcium-Activated Potassium Channels - genetics ; Messenger RNA ; Mitochondria ; mRNA ; Neurons ; Polymerase chain reaction ; Potassium ; Potassium channels ; Potassium channels (calcium-gated) ; Proteins ; Rats ; Ribonucleic acid ; RNA ; RNA, Messenger ; siRNA ; Small interfering RNA ; Splicing</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2010-12, Vol.107 (49), p.21152-21157</ispartof><rights>Copyright National Academy of Sciences Dec 7, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-96d9ef5d4e8ecaa54224e8b01ec451cce9a7ebe08a66863c6b68ef0a90da88d3</citedby><cites>FETCH-LOGICAL-c596t-96d9ef5d4e8ecaa54224e8b01ec451cce9a7ebe08a66863c6b68ef0a90da88d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/107/49.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25756847$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25756847$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21078998$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bell, Thomas J.</creatorcontrib><creatorcontrib>Miyashiro, Kevin Y.</creatorcontrib><creatorcontrib>Sul, Jai-Yoon</creatorcontrib><creatorcontrib>Buckley, Peter T.</creatorcontrib><creatorcontrib>Lee, Miler T.</creatorcontrib><creatorcontrib>McCullough, Ron</creatorcontrib><creatorcontrib>Jochems, Jeanine</creatorcontrib><creatorcontrib>Kim, Junhyong</creatorcontrib><creatorcontrib>Cantor, Charles R.</creatorcontrib><creatorcontrib>Parsons, Thomas D.</creatorcontrib><creatorcontrib>Eberwine, James H.</creatorcontrib><title>Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We report that stress axis—regulated exon (STREX)-containing calcium-activated big potassium (BKCa) channel splice variant expression and physiology are regulated in part by cytoplasmic splicing and intron retention. NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons.</description><subject>Action potentials</subject><subject>Alternative splicing</subject><subject>Alternative Splicing - genetics</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Calcium</subject><subject>Cells</subject><subject>Data processing</subject><subject>Dendrites</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Exons</subject><subject>Gene expression</subject><subject>Hippocampus</subject><subject>Hippocampus - cytology</subject><subject>Immunocytochemistry</subject><subject>Introns</subject><subject>Introns - genetics</subject><subject>Large-Conductance Calcium-Activated Potassium Channels - genetics</subject><subject>Messenger RNA</subject><subject>Mitochondria</subject><subject>mRNA</subject><subject>Neurons</subject><subject>Polymerase chain reaction</subject><subject>Potassium</subject><subject>Potassium channels</subject><subject>Potassium channels (calcium-gated)</subject><subject>Proteins</subject><subject>Rats</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger</subject><subject>siRNA</subject><subject>Small interfering RNA</subject><subject>Splicing</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9rFDEUx4Modls9e1IGL57GJjP5eRGkaC0UvPQe3mTetlmymTHJLPS_N8uuXfXSUx4vn_eB9_gS8o7Rz4yq_nKOkGvFRCd5bbwgK0YNayU39CVZUdqpVvOOn5HznDeUUiM0fU3OuspqY_SKhJtY0hSbhAVj8bVag_PBFyiYmzwH77DZQfIQSzP6Habsy2PjY-MgOL9sW3DF7yo9NoO_b-apQM6137gHiBFD7cxLgL06vyGv1hAyvj2-F-Tu-7e7qx_t7c_rm6uvt60TRpbWyNHgWowcNToAwbuulgNl6LhgzqEBhQNSDVJq2Ts5SI1rCoaOoPXYX5AvB-28DFscXV0sQbBz8ltIj3YCb__9if7B3k8729cLdZxXwaejIE2_FszFbn12GAJEnJZstepYp3tqnidFz5WkQj9PMqlMz4yq5Mf_yM20pFgPViHFZK81rdDlAXJpyjnh-mk9Ru0-GnYfDXuKRp348PdVnvg_WahAcwT2kyedstxUqooq8v6AbHKZ0kkhlJCaq_43DM7MoA</recordid><startdate>20101207</startdate><enddate>20101207</enddate><creator>Bell, Thomas J.</creator><creator>Miyashiro, Kevin Y.</creator><creator>Sul, Jai-Yoon</creator><creator>Buckley, Peter T.</creator><creator>Lee, Miler T.</creator><creator>McCullough, Ron</creator><creator>Jochems, Jeanine</creator><creator>Kim, Junhyong</creator><creator>Cantor, Charles R.</creator><creator>Parsons, Thomas D.</creator><creator>Eberwine, James H.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20101207</creationdate><title>Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations</title><author>Bell, Thomas J. ; 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NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>21078998</pmid><doi>10.1073/pnas.1015264107</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Action potentials Alternative splicing Alternative Splicing - genetics Animals Biological Sciences Calcium Cells Data processing Dendrites Deoxyribonucleic acid DNA Exons Gene expression Hippocampus Hippocampus - cytology Immunocytochemistry Introns Introns - genetics Large-Conductance Calcium-Activated Potassium Channels - genetics Messenger RNA Mitochondria mRNA Neurons Polymerase chain reaction Potassium Potassium channels Potassium channels (calcium-gated) Proteins Rats Ribonucleic acid RNA RNA, Messenger siRNA Small interfering RNA Splicing |
| title | Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations |
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