؈ޏkdǂRNA^pN

<strong>͌ sY</strong>
iww@wn `q@\wj
emailF<a href="mailto:ykawahara@rna.med.osaka-u.ac.jp">͌sY</a>
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̈Zr[, <strong>2</strong>, e010 (2013)@<a href="http://dx.doi.org/10.7875/leading.author.2.e010">DOI: 10.7875/leading.author.2.e010</a>
Yukio Kawahara: <strong>Amyotrophic lateral sclerosis and RNA-binding proteins.</strong>

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<h2>v </h2>
@؈ޏkdǂ͏ʂщʂ̉^j[IIɕϐSg̋ؗ͂ቺĂ_oałDߔNCTDP-43FUSȂǁC@\\ɋʐ̂RNA^pN̕aԂɐ[֗^Ă邱Ƃ炩ɂȂĂDƂɁCϐj[ɔF߂TDP-43ẑ͌̕ǔ܂߂啔̋؈ޏkdǂɋʂałCTDP-43͔ǂѕaԂ̌ɂĂD܂C`qƓ肳悤ɂȂC̈ꕔ͑OtϐǂƂ΂s𐫎Ɠ̎XyNgɂ邱ƂĂD݁C؈ޏkdǂɂẮCRNA^pNɋʂ@\WIُ̐Ƃϓ_ƁC^pN𒆐SƂÏŴ̌`ɂŐƂϓ_̗ʂ猤i߂ĂDł́C؈ޏkdǂ̌̍ŐV̓ɂāCƂɁCRNA^pNRNAӂɂ^pNɏœ_ĉD

<h2>͂߂</h2>
@؈ޏkdǁiamyotrophic lateral sclerosisFALSj͉^j[IIɕϐSg̋ؗ͂ቺĂ_oałDN̂ɔǂP[XC񔭏ǂƂ̐is͑C͐NŌċzsSɂD炩Ȉ`P[X͑Ŝ1قǂŁC͌ǔłD1NԂ̐VK̔ǎ҂͐l10l1lŁC킪ɂ9000l̊҂݂DˑRƂčÖ@͂ȂD2006N܂ł́C`̋؈ޏkdǂ̌Ƃē肳ꂽ`q<em>SOD1</em>`q<em>ALS2</em>/<em>Alsin</em>`qȂǂĂC܂C啔߂ǔ̋؈ޏkdǂ̔ǋ@\ɂāČ`qǂ܂łĂ̂Ƃc_ȂDC2006NCTDP-43iTAR DNA-binding protein of 43 kDajƂ΂RNA^pNCϐj[̍זÊ̕ɂărL`Cُȃ_CfЉȂǂ̏C~ςĂ邱Ƃ<a href="#R1"><sup>1,2)</sup></a>C_@ɁC؈ޏkdǂ̌͑傫iWDƂɁCV[NGT[̎pɂƂȂ̎łψو`q𓯒ł悤ɂȂƂSGL\͂eՂɂȂƂɂC؈ޏkdǂ̔ǂƊ֘A`qψقƕ񍐂悤ɂȂD2009Nȍ~CN3`5قǂ̐VK̈`qψق肳ĂCŜł20Ă<a href="#R3"><sup>3)</sup></a>D̂Ȃɂ͍\Iɗގ̍RNA^pNR[h`q܂܂ĂCRNA^pNȂ炩ُ̈킪؈ޏkdǂ̔ǂ̌ɂƍl悤ɂȂĂD

<h2>1D؈ޏkdǂTDP-43</h2>
@TDP-43ϐj[̍זÊ̕ɒ~ςĂƂ<a href="#R1"><sup>1,2)</sup></a>C؈ޏkdǂ̌ɑ̃p_CVtg炵D
@1ڂ́Cl̕as𐫎̈łOtϐǁifrontotemporal lobar degenerationFFTLDj̈ꕔɂoꂽƂłDɁC̔܂ȂCpx͂߂Ă܂ȂC؈ޏkdǂёOtϐǂ̈ꕔɂTDP-43R[h<em>TARDBP</em>`q̕ψق肳ꂽ<a href="#R4"><sup>4,5)</sup></a>i<a href="#F1">}1</a>jD̂߁C؈ޏkdǂƑOtϐǂ̈ꕔ͂ЂƂ̎XyNgƂĂƂ炦悤ɂȂCƂɁCTDP-43ẑ̕ƂȂP[XTDP-43^pNǁiTDP-43 proteinopathyjƂ΂悤ɂȂDȂ킿C؈ޏkdǂ̊҂ɂ͐isƂƂɒs悷P[XC܂tɁC͂ߒs𔭏ǂ̂ɋ؈ޏkdǂ̏Ǐ悷ꍇ邱ƂC`qĂĂǏ̔ǂisɂ͂΂̂邱Ƃ킩ĂD܂C܂ŋ؈ޏkdǂɂĂ͍זÊ傫CȂǌ`ԓIȓِOɂ^j[̑IIȐƎ㐫lĂC]玿̃j[ɂƎ㐫Ƃϓ_ŗގj[邱ƂC̃j[ɋʂqlKvłĂD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@؈ޏkdǂ܂͑Otϐǂɂĕ񍐂ĂTDP-43̕ψ</strong>
ψق̈ʒuԐF̊ۂŎD
RRMFRNA`[tCGRDFOVb`hCD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.1.png&amp;caption=fig1-caption-text]

@2Ԗڂ́C<em>SOD1</em>`q̕ψقŐ`؈ޏkdǂȂǈꕔCTDP-43ẑ͈̕`邢͌ǔɂ炸قƂǂ̋؈ޏkdǂɋʂĔF߂ał邱Ƃoꂽ_ł<a href="#R1"><sup>1,2,6)</sup></a>D܂ŁC̑啔߂ǔ̋؈ޏkdǂɂĂ͕aԂɂ܂肪ɖRCTDP-43͂قƂǂ̋؈ޏkdǂɋʂ锭ǂɊ֗^錮^pNƂĔF悤ɂȂD
@3ڂ́C{CTDP-43͖9jɋǍ݂Ă邪Cϐj[ɂĂ͂قƂǂׂĂזÊ̕ɒ~ςjĂƂaꂽƂł<a href="#R1"><sup>1,2)</sup></a>DāCϐj[ɂẮC{Cjł͂ĂTDP-43̐Iȋ@\͑rĂ͂łD̂߁Ĉ\TDP-43ÏŴŐ𔭊זEɂƂŐ̊l̖ʂƁCTDP-43̋@\ُ̈ƂʂaԂ̌WJ悤ɂȂD

<h2>2DTDP-43̋@\ƕa</h2>
@V[NGT[gԗIȉ͂ɂ΁CTDP-436000ȏRNA40,000ȏ̕ʂɌĂƂ<a href="#R7"><sup>7,8)</sup></a>DUGz̖Lxȗ̈ɍDŌCʂ̑啔̓Cgɂ<a href="#R7"><sup>7,8)</sup></a>DTDP-43͂WIƂȂRNÃvZVO܂܂ȃXebvŐ䂵ĂC]ʁCXvCVOCRNAACRNÄ艻ɂ킦C}CNRNA̔̑iȂǁC̋@\͑lł<a href="#R9"><sup>9-11)</sup></a>i<a href="#F2">}2a</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@TDP-43̋@\TDP-43זE̗Ű@\</strong>
iajTDP-43́C]ʁCXvCVOCRNAACRNÄ艻C}CNRNA̔iĚoHj̑iȂǁClȋ@\D
ibjTDP-43͂ɊjɋǍ݂Ă邪C؈ޏkdǂёOtϐǂł͊jזEɂċÏWD̂߁CTDP-43̊jɂ@\̑rƁCזEɂÏŴ̌`ɂŐɂCIɍזEЂNƍlĂD
TDP-43̃IWF́̕CvIlhCD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.2.png&amp;caption=fig2-caption-text]

@쐶^̃qgTDP-43ߏɔgXWFjbN}EX́C^j[̕ϐɂ؈ޏkdǗl̏Ǐ悷D܂COtϐǂɂĔF߂悤ȑ]玿̃j[̕ϐF߂<a href="#R12"><sup>12)</sup></a>DɁCTDP-43ẑ̕`CfЉTDP-43̒~ςF߂DlɁC`̋؈ޏkdǂɂē肳ꂽψٌ^TDP-43𔭌gXWFjbN}EXC؈ޏkdǗl̏Ǐ悷<a href="#R13"><sup>13)</sup></a>D̏́C^j[ȂǓ̃j[TDP-43̕ψق̗Lɂ炸CƂɁCTDP-43̉ߏȏԂɐƎł邱ƂĂD
@TDP-43זE̗Ű@\ɂẮCɏqׂ悤ɁCŐ̊lƋ@\ُ̈Ƃ2̍lD܂O҂ɂẮCTDP-43C[̗̈ɃvIlhCۗLĂÏW₷̂邱ƂɗR<a href="#R14"><sup>14,15)</sup></a>i<a href="#F1">}1</a>jDƂɁC̒fЉɂYC[̒fЂ͋ÏW̌ߕ̂ɒ~ς₷ƍli<a href="#F2">}2b</a>jDۂɁC|{זEC[̒fЂ𔭌ƋÏŴ`זEU<a href="#R16"><sup>16)</sup></a>D܂C؈ޏkdǂɂē肳Ă<em>TARDBP</em>`q̕ψق̂قƂǂC[̗̈ɏWĂCψقƂɈ艻ÏW₷Ȃ邱ƂmĂ<a href="#R17"><sup>17,18)</sup></a>i<a href="#F1">}1</a>jDɁCvIâ悤ɁCזEɂċÏWTDP-43ق̍זEɂ`ċÏW𑣐i\Ă<a href="#R15"><sup>15)</sup></a>DāCqgTDP-43ߏɔgXWFjbN}EX̂悤TDP-43ÏW₷󋵂ƂȂ΁CƒfЉƋÏŴ̌`ɂŐ^j[ɊgÛŁCŐlł͋ÏŴ̌`ɂƂȂזE̗U؈ޏkdǂ̕aԂ̎vȌł͂Ȃƍli<a href="#F2">}2b</a>jD
@ŁCTDP-43jזÊ̕ւƈڍsƁC{CjɂĂ͂Ă@\͑r邱ƂCTDP-43ɂRNÄُ킪זE̎vȌłƂli<a href="#F2">}2b</a>jDہC^j[ɓٓITDP-43̃mbNAEg}EX͔Ӕɋ؈ޏkdǗl̏Ǐ悷<a href="#R19"><sup>19)</sup></a>D܂CTDP-43זÊ̕Ɉڍs܂̒iKRNAɈُĂ邱Ƃ鏊邱Ƃ<a href="#R10"><sup>10,20)</sup></a>CÏŴ̌`͍זẾCIȃj[̕ϐ̌TDP-43̋@\ُ̈ɂ\ĂDɂĂł́CȂ^j[ȂǓ̃j[TDP-43̉ߏȏԂɐƎł̂C܂C؈ޏkdǂ̊҂̉^j[ɂTDP-43̑ӂɏIɂǂ̂悤Ȉُ킪Ă͉̂ĂȂDɁCTDP-43̋@\ُ̈킪Iȃj[̕ϐ̌łȂCٓITDP-43̋@\邢͂̕WI^j[ɑ݂Ɨ\z邱ƂC炪肳ΕaԂ̉𖾂ɂނ傫OiƍlD

<h2>3D؈ޏkdǂFETt@~[</h2>
@2009NC`؈ޏkdǂ̌`qƂ<em>FUS</em>ifused in sarcomaj`q肳ꂽ<a href="#R21"><sup>21,22)</sup></a>i<a href="#F3">}3</a>jD̈`q̎YFUSTDP-43ƓlRNA^pNł邱ƁCOtϐǂ̈ꕔ<em>FUS</em>`q̕ψق肳ꂽƂC؈ޏkdǂёOtϐǂ̕aԂɂ͋ʂRNA^pN֗^̂ł͂Ȃƍl悤ɂȂDFUS͊jɂ葽Ǎ݂邪CTDP-43ƔׂƍזEɋǍ݂銄͑D܂C5500ȏRNA44,000ȏ̕ʂɌ邱ƂmĂCXvCVOmRNÄ艻ȂRNA̋@\ɑlɊ֗^Ă<a href="#R23"><sup>23-25)</sup></a>DȂC܂ɂTDP-43Ƃ͕WI⌋ʂ͈قȂĂCʂWI͂Ă<a href="#R23"><sup>23,24)</sup></a>D؈ޏkdǂɂē肳ĂψقN[̃vIlhCC[̊jǍ݉VOi̕t߂ɑ<a href="#R26"><sup>26)</sup></a>i<a href="#F3">}3</a>jDjǍ݉VOȋɐψقFUS̋Ǎ݂jזEւƕς邱ƂC̕ψق҂͂葁ɔǂXɂ<a href="#R27"><sup>27)</sup></a>D܂CTDP-43ƓlɁCvIlhC邽ߋÏŴ`₷C<em>FUS</em>`q̕ψقƂȂ؈ޏkdǂł͑̃P[XɂFUSẑ̕F߂<a href="#R21"><sup>21,22)</sup></a>DŁCFUSẑ̕P[XłTDP-43ُ̈ƂȂȂƁC<em>FUS</em>`qɕψقȂOtϐǂłFUSẑ̔̕F߂P[X̂邱Ƃ<a href="#R28"><sup>28)</sup></a>C؈ޏkdǂёOtϐǂɂTDP-43ɈˑȂFUSǂ̕aԂƍlĂDہC쐶^̃qgFUSߏɔgXWFjbN}EX͖Ⴢ𐶂3JŎɂ<a href="#R29"><sup>29)</sup></a>D܂Cψٌ^̃qgFUS̔𐶌ォUbgł͐70ŖჂ𐶂ɂ<a href="#R30"><sup>30)</sup></a>D̂悤ɁCTDP-43ƓlɁCfɂĂ͕ψق̗Lɂ炸FUS̉ߏ蔭ɂ^j[ɏǏ悷D

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@FETt@~[̍\Ƌ؈ޏkdǂɓٓIȕψ</strong>
ψق̈ʒuԐF̊ۂŎD
SYGQFZ-`V-OV-O^~b`hCCGRDFOVb`hCCRRMFRNA`[tCRGGFAMj-OV-OVs[gb`hCD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.3.png&amp;caption=fig3-caption-text]

@FUS͍\Iɋ߂TAF15iTATA-binding protein associated factor 15jEWSR1iEwing sarcoma breakpoint region 1jƂƂFETt@~[\i<a href="#F3">}3</a>jD͍\Iɋ߂łȂC܂܂ȂɂĐF̓]̐₷̈ɂƂ_킹<a href="#R26"><sup>26)</sup></a>D̂߁C<em>TAF15</em>`q<em>EWSR1</em>`qɂĂψى͂i߂C؈ޏkdǂɂēٓIȕψق肳ꂽ<a href="#R31"><sup>31,32)</sup></a>i<a href="#F3">}3</a>jD܂CFETt@~[ɂ͋ʂăvIlhC݂邽ߋÏW₷XɂC{͂ɊjɋǍ݂ĂFETt@~[^pN͕ϐj[ɂĂ͍זEɈڍsĂD̂悤ɁCTDP-43FETt@~[ɂĂ͕aɂĂ݂͑ɔrIł邪C\␶Iȋ@\ɂĂ͋ʓ_C؈ޏkdǂ̔ǂɂoH͂x܂ŗގĂ̂ł͂ȂƗ\zDɊւĂCTDP-43FETt@~[Ƃ̂ɂ͋ʂRNA̋@\WIRNACُ̐̈ɂ؈ޏkdǂ͔ǂ̂ł͂ȂƂlƁC\IȗގƂɋÏW₷CɂŐl̂ł͂ȂƂlD

<h2>4D؈ޏkdǂƃs[gzُ̈ȐL</h2>
@2010N2011NɂāC؈ޏkdǂ̕aԂl邤ŁCȂdvȔD܂ŁC`Ґ]ϐǂ؋ْWXgtB[ȂǂɂẴ͓s[gzُ̈ȐLł邱ƂmCs[gaƂ΂ĂDƂɁCHuntingtonaȂǂł̓^pNR[ḧɐCAGs[gzُ̈ȐL|O^~ւƖ|󂳂邱ƂC|O^~aƑ̂D؈ޏkdǂ͂s[gz̐LƂ͖ƍlĂC2010NC|O^~äł`Ґ]ϐ2^̌ƂȂ<em>ATXN2</em>`qiAtaxin-2R[hjCAGs[gz񂪁C؈ޏkdǂ̊҂ɂėLӂɐLĂ邱Ƃ񍐂ꂽ<a href="#R33"><sup>33)</sup></a>D҂͂̃s[g̉񐔂23ȉł̂ɑ΂C`Ґ]ϐ2^̊҂ł34ȏɐLĂDŁC؈ޏkdǂ̊҂ł͂̒Ԃ̒C27`33̃s[gۗLĂP[XLӂɑD̂̂CHuntingtona`Ґ]ϐ1^Ȃǂق̃s[gǎƂȂ`q̃s[g̉񐔂Ƌ؈ޏkdǂ̔ǂƂ̑ւ͂ꂽCLӂȑւ<em>ATXN2</em>`q݂̂ŔF߂ꂽ<a href="#R34"><sup>34)</sup></a>ĎʂCAtaxin-2؈ޏkdǂ̔ǂɊ֗^Ăƍl悤ɂȂCł́CCAGs[gz̒x̐Lŋ؈ޏkdǂǂ邩ǂ͕słCǂ߂댯qƂĔFĂDAtaxin-2̓|A^pNłPABPC1ƒڂɌ邱ƂȂ炩RNAӂɊ֗^ĂƍlĂC܂CTDP-43Ataxin-2RNAĂ<a href="#R33"><sup>33,35)</sup></a>DVEWEoG̊TDP-43ߏɔƐ_oϐ邪CɂAtaxin-2ߏɔƐ_oϐ͉邱ƂCAtaxin-2TDP-43_oϐ̕q@\𑣐i@\ƐĂ<a href="#R33"><sup>33)</sup></a>D
@2011NC<em>C9orf72</em>`q̃CgɂGGGGCCs[gzُ̈ȐLꕔ̋؈ޏkdǂёOtϐǂ̌Ƃē肳ꂽ<a href="#R36"><sup>36,37)</sup></a>D̈`qψق͉ĂɂĔrIC`؈ޏkdǂ30`40Cǔ؈ޏkdǂ5`8ɔF߂ꂽC킪ł͂߂ďłƂ狭nnҌʂz肳ꂽDC{̋Iɔɂ͋؈ޏkdǂ̑n̂邱ƂmĂ邪C̈ꕔ<em>C9orf72</em>`qGGGGCCs[gzُ̈ȐLƂmFꂽ<a href="#R38"><sup>38)</sup></a>DNɂ킽C؈ޏkdǂ̑闝RɂĂ͂܂܂ȉ񏥂Ăo܂Č̈[炩ɂȂӋ`͑傫D
@̔ɂC؈ޏkdǂƑOtϐǂƂXyNgɂ邱ƂĔF邱ƂɂȂłȂC؈ޏkdǂёOtϐǂق̃s[gaƋʂǋ@\\l悤ɂȂDs[gał͈ʂɁCs[gz񂩂|󂳂ꂽ^pNŐ𔭊ꍇƁCs[gz܂RNÂ̂Ő𔭊ꍇƂmĂ邪CߔNł́C̃s[gaɂĂ̗҂IɊ֗^Ăƍl悤ɂȂĂĂDۂɁC؈ޏkdǂёOtϐǂɂẮCC<em>C9orf72</em>`qGGGGCCs[gz̓Cgɂ邱Ƃ炱̃s[gz܂RNAŐ𔭊ƍlC܂܂RNA^pNzČ`זE\̂łRNAÏẂiRNA focij̊ώ@邱Ƃ񍐂ꂽ<a href="#R36"><sup>36,37)</sup></a>i<a href="#F4">}4</a>jD̂̂Cs[gzɊ֘AJnRhłATG̔񑶍݉ɂĊJnȌ`ł̖|irepeat-associated non-ATG-initiated translationCRAN|j@\āC<em>C9orf72</em>`qGGGGCCs[gz̈悩^pNĂ邱Ƃꂽ<a href="#R39"><sup>39)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/6559" target="_blank">V_r[</a> łfځji<a href="#F4">}4</a>jD<em>C9orf72</em>`qGGGGCCs[gz񂪈ُɐLĂ銳҂̔]ɂẮCTDP-43ẑ̕ƂƂTDP-43Â̕F߂邪CTDP-43Â̕ɂGGGGCCs[gz񂩂|󂳂ꂽ^pNÏWĂ邱Ƃ炩ɂȂ<a href="#R39"><sup>39)</sup></a>D́C<em>C9orf72</em>`qGGGGCCs[gz̐Lǂ̂悤TDP-43̋@\Ǎ݂ɉêC̕q@\炩ɂȂ΁C؈ޏkdǂ̑SʂɋʂTDP-43ǋ@\̏㗬ɂ܂邱ƂłƊ҂D

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@<em>C9orf72</em>`qGGGGCCs[gzُ̈ȐLƍזE̗Ű@\</strong>
RBDFRNA^pND
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2013/09/Kawahara-2.e010-Fig.4.png&amp;caption=fig4-caption-text]


<h2>5D؈ޏkdǂƑn^pN</h2>
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<h2></h2>
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<h2> </h2>
<ol>
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</ol>
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<span class="author">͌ sYiYukio Kawaharaj</span>
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