The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    1/20

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    http://elife.elifesciences.org/http://dx.doi.org/10.7554/elife.00048http://dx.doi.org/10.7554/elife.00048.001http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://dx.doi.org/10.7554/elife.00048.001http://dx.doi.org/10.7554/elife.00048http://creativecommons.org/licenses/by/3.0/http://www.elifesciences.org/the-journal/open-access/http://elife.elifesciences.org/
  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    2/20

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    http://dx.doi.org/10.7554/elife.00048http://dx.doi.org/10.7554/elife.00048.002http://dx.doi.org/10.7554/elife.00048.002http://dx.doi.org/10.7554/elife.00048
  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    3/20

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    http://dx.doi.org/10.7554/elife.00048http://dx.doi.org/10.7554/elife.00048
  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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    Djii flmimk|

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    http://dx.doi.org/10.7554/elife.00048http://dx.doi.org/10.7554/elife.00048.003http://dx.doi.org/10.7554/elife.00048.004http://dx.doi.org/10.7554/elife.00048.005http://dx.doi.org/10.7554/elife.00048.006http://dx.doi.org/10.7554/elife.00048.007http://dx.doi.org/10.7554/elife.00048.007http://dx.doi.org/10.7554/elife.00048.006http://dx.doi.org/10.7554/elife.00048.005http://dx.doi.org/10.7554/elife.00048.004http://dx.doi.org/10.7554/elife.00048.003http://dx.doi.org/10.7554/elife.00048
  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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    Djii flmimk|

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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    imk ~botj "Clkzvj 0d, oe` jeboedj` djii `jopb "Clkzvj 0`,) le`ldoplek pbop Fl~? gVEO ~vmdjttlek lt

    lg~mvpoep mv golepolelek djii pejtt le pbj odj m JV tpvjtt% F| dmepvotp pm djii kvm{pb le ilqzl` dzi'

    pzvj) Fl~? gzpoep djiit kvj{ me Z^V'le`zdlek pzeldog|dle ~iopjt mei| govkleoii| {mvtj pbop {li` p|~j

    djiit "Clkzvj 0ckzvj tz~~ijgjep 4,% Pbj lg~mvpoedj mFl~? gVEO ~vmdjttlek) pbjvjmvj) sovljt

    {lpb kvm{pb dme`lplmet%

    @ltdzttlme[j bosj fjkze pm dbovodpjvlxj pbj Z^V le ttlme |jotp% Pm mzv tzv~vltj) {j ltdmsjvj` pbopf| dmepvotp

    pm oii mpbjv jzaov|mpjt tpz`lj` pm `opjT% ~mgfj `mjt emp zplilxj Lvj?) pbj gmtp oedljep JV tpvjtt

    tjetmv) pm dmepvmi pvoetdvl~plme% Vopbjv) T% ~mgfj jrdiztlsji| vjiljt me p{m gjoet m Lvj?'`j~je`je

    ~mtp'pvoetdvl~plmeoi vjkzioplme pm dm~j {lpb JV tpvjtt8

    l% Vjkziopj` Lvj?'`j~je`jep gVEO `jdo| "VL@@, m o iovkj oe` blkbi| tjijdp tjp m gVEOt)

    oii m {bldb ovj ~vj`ldpj` pm fj pvoetiopj` f| gjgfvoej'fmze` vlfmtmgjt op pbj JV% Pbj

    gjdboeltpld jopzvjt m gVEO `jkvo`oplme le T% ~mgfj ovj blkbi| vjgleltdjep m VL@@

    ~vjslmzti| `jtdvlfj` le letjdp oe` goggoiloe djiit) {bjvj lp oddmg~oeljt Lvj?'`j~je`jep

    gVEO t~ildlek%

    ll% ^vmdjttlek mFl~? gVEO {lpble lpt 4 ZPV) ijo`lek pm imtt m lpt ~mi|O poli) {bldbdmzepjv'

    lepzlplsji|vjtzipt le lpt tpoflilxoplme% Pbj gjdboeltpld jopzvjt m pblt ze~vjdj`jepj` gVEO

    ~vmdjttlek tpj~ vjtjgfij pbj lelploi Lvj?'`j~je`jep ezdijmi|pld tpj~ m VL@@ fzp Fl~? gVEO

    pbje jtdo~jt zvpbjv `jdo|%

    Mzv vjtzipt tblej ej{ ilkbp me bm{ JV bmgjmtpotlt doe fj golepolej` oe` ze`jvtdmvj pbj otdleop

    lek `lsjvkjedj m tmizplmet pbop `ljvjep t~jdljt jsmisj` pm odbljsj pblt pota%

    Pbj ~b|tlmimkldoi vmij m VL@@ le T% ~mgfjJV tpvjtt ovltjt vmg letzdljedljt le boe`ilek pbj ~vmpjle'mi`lek imo` le pbj JV izgje

    Bmgjmtpotlt) pbjvjmvj) doe fj vjjtpofiltbj` le p{m ~vledl~oi {o|t8 ledvjotlek pbj do~odlp| m pbj

    JV pm boe`ij pbj imo`mv `jdvjotlek pbj imo` pm gjjp pbj do~odlp|% Bjvj {j tbm{ pbop gVEO

    `jdo| doe tjvsj ot pbj tmij gjoet m vjtmislek JV tpvjtt {lpbmzp pvoetdvl~plmeoi z~'vjkzioplme m

    diottldoi Z^V povkjp kjejt% Pbj l`jeplj` pvoetdvl~pt povkjpj` mv VL@@ dmg~mtj o tzftjp m

    gVEOt) oii jedm`lek ~vmpjlet pbop vjtl`j le mv pvosjvtj pbj tjdvjpmv| ~opb{o|% Fjlek pvoetiopj` f|

    gjgfvoej'fmze` vlfmtmgjt) pbjtj gVEOt ovj pbjvjmvj le oe o~~vm~vlopj djiiziov imdoplme pm

    gjjp odplsopj` Lvj?%Ot oii ~vmpjlet jedm`j` f| VL@@ povkjp gVEOt jepjv pbj JV izgje) pbjlv t|epbjtlt f| `jelplme

    dmepvlfzpjt pm pbj fzv`je m pbj JV ~vmpjle mi`lek godblejv|% VL@@ pbjvjmvj bji~t vj`zdj pbj

    ~vmpjle'mi`lek imo`% Lp lt ijtt dijov bm{jsjv {bjpbjv tzdb vj`zdplme {mzi` bosj o gohmv lg~odp

    Le`jj`) o foda'm'pbj'jesjim~j doidzioplme le`ldopjt pbop le T% ~mgfj VL@@ vj`zdjt pbj pmpoi ~vmpjle

    leczr lepm pbj JV f| mei| ?:*) jsje ze`jv pbj tjsjvj JV tpvjtt dme`lplmet jr~imvj` bjvj jr~jvlgje

    poii|% Pblt jtplgopj `jvlsjt vmg mzv vlfmtmgj mmp~vleplek `opo le emvgoi st JV'tpvjttj` djiit8 [j

    tdmvj` pbj vjioplsj pvoetioplmeoi jekokjgjep m oii gVEOt jedm`lek ~vmpjlet `lt~io|lek tlkeo

    tjqzjedjt mv pvoetgjgfvoej vjklmet pm jtplgopj czr m ej{i| t|epbjtlxj` ~mi|~j~pl`jt le pm pbj JV

    oe` doidziopj` pbj lg~odp m VL@@ me pblt tjp "tjj Gopjvloit oe` gjpbm`t,% Lp lt `ldzip pm jesltlme

    bm{ o gjvj ?:* vj`zdplme m fzia ~vmpjle czr lepm pbj JV {mzi` tzdj pm oiijslopj oe mpbjv{ltj

    ijpboi JV tpvjtt%

    Lp lt ~mttlfij pbop VL@@ ~vjjvjeploii| povkjpt ~vmpjlet pbop ovj ~ovpldziovi| `ldzip pm mi` oe`

    bjedj glkbp bosj o `lt~vm~mvplmeoi lg~odp me pbj ~vmpjle mi`lek imo` le pbj JV izgje% Le`jj`)Lvj? go| fj imdoilxj` pm pbj sldlelp| m gVEOt jedm`lek tzdb ~vmpjlet f| lepjvodplmet m lpt JV

    izgjeoi zemi`j` ~vmpjle tjetlek `mgole {lpb ~mvplmet m pbj eotdjep ~mi|~j~pl`j dbolet pbop

    bosj jepjvj` pbj JV izgje) ot ~vjslmzti| ~vm~mtj` "Bmiilje oe` [jlttgoe) 6>>31 Vme) 6>>3,

    Oe oipjveoplsj oe` emp gzpzoii| jrdiztlsj slj{ ~mtjt pbop VL@@ qzoilpoplsji| dboekjt pbj kjej jr~vjt

    tlme ~vmij% Le tz~~mvp m pblt emplme) {j empldj pbop pbj ~m~zioplme m VL@@ povkjp gVEOt lt blkbi|

    tjijdplsj% gVEOt jedm`lek ~vmpjlet lesmisj` le il~l` gjpofmiltg ovj blkbi| jevldbj` "4?* m VL@@

    povkjp gVEO ot dmg~ovj` pm 3%;* le oii JV'povkjpj` gVEOt,% Gmvjmsjv) {j e` pbop VL@@ povkjpt

    jedm`lek ~vmpjlet lesmisj` le tpjvmi gjpofmiltg ovj ~ovpldziovi| jevldbj` "?4* ot dmg~ovj` pm ?%4*,

    Bm{ vj`zdj` tpjvmi t|epbjtlt {mzi` dmzepjvodp pbj pmrld jjdpt m JV tpvjtt vjgolet zedijov% Mej

    http://dx.doi.org/10.7554/elife.00048http://dx.doi.org/10.7554/elife.00048
  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    12/20

    Djii flmimk|

    Algglk jp oi% jIlcj 6>?61?8j>>>02% @ML8 ?>%;::0-jIlcj%>>>02 ?6 mc 6>

    Vjtjovdb ovpldij

    ~mttlfij jr~ioeoplme {mzi` fj pbop JV tpvjtt ilglpt tpjvmi jrlp pbvmzkb sjtldziov pvoet~mvp oe` o dmg

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    VL@@ f| Lvj? oe` zvpbjv `jdo| go| fj mfilkopmvli| dmz~ij`%

    ^vmdjttlek mFl~? gVEOPbj mftjvsoplme pbop T% ~mgfj Fl~? gVEO dboekjt tlxj z~me JV tpvjtt `opjt foda pm ?

  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    13/20

    Djii flmimk|

    Algglk jp oi% jIlcj 6>?61?8j>>>02% @ML8 ?>%;::0-jIlcj%>>>02 ?4 mc 6>

    Vjtjovdb ovpldij

    bjvj) Fl~? gVEO lt oitm dijosj` f| Lvj?) |jp jtdo~jt `jdo|% Pbj Lvj? dijosokj tlpj tbovjt pbj togj

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    Govxiz) 6>>6,%

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    tzfhjdp pm pblt zelqzj vjkzioplme% [b| {mzi` tzdb o tlekziov gjdboeltg bosj jsmisj` jrdiztlsji| m

    Fl~?= Cvmg {mva le mpbjv t~jdljt) Fl~? jgjvkjt ot pbj gmtp ~ijlmpvm~ldoii| lg~mvpoep oe` ~vjdltji|

    dmepvmiij` JV dbo~jvmej "Kzim{ jp oi%) 6>>6,% Gmvjmsjv) Fl~? bmi`t o zelqzj ~mtlplme le T% ~mgfj

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    le T% ~mgfj) ot le mpbjv t~jdljt) jeboedjt pzvemsjv m ki|dmt|iopj` ~vmpjlet oe` pbop pbj vjkzioplme m

    Fl~? gVEO lt fjejdloi pm lpt tpoflilp| f| dmg~jetoplek mv tzdb imtt "Fjveotdmel jp oi%) 6>?6,%

    Dmediztlmet

    Cvmg oe jsmizplmeov| oekij) pbj Z^V le T% ~mgfj ~vmsl`jt oe lepvlkzlek jrog~ij m bm{ gmijdziogodblejt doe fj vj~zv~mtj`% [blij le~zp "zemi`j` ~vmpjlet) JV tpvjtt, oe` mzp~zp "VEO dijosokj,

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    {o|t) ot lp lt pbj dotj le djiit jr~jvljedlek ~vmimekj` oe` zeglplkopj` JV tpvjtt "Boe jp oi%) 6>>

  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    14/20

    Djii flmimk|

    Algglk jp oi% jIlcj 6>?61?8j>>>02% @ML8 ?>%;::0-jIlcj%>>>02 ?0 mc 6>

    Vjtjovdb ovpldij

    Gopjvloit oe` gjpbm`t

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    `jtdvl~pmv pm pbj kjej eogj% ^vmpjlet ovj le`ldopj` le Vmgoe ijppjvt%

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    "Gmvjem jp oi%) ?

  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    15/20

    Djii flmimk|

    Algglk jp oi% jIlcj 6>?61?8j>>>02% @ML8 ?>%;::0-jIlcj%>>>02 ?: mc 6>

    Vjtjovdb ovpldij

    Kvm{pb otto| oe` dmime| mvglek zelp otto| mv Fl~? 4 ZPV gzpoep[P oe` Fl~?"PPOODPKKPKD,gzpoep djiit {jvj kvm{e msjvelkbp le "\J:T, gj`lo% Pbj ejrp gmvelek

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    "? gi ~jv {jii, msjv 46 bv op 46D% Pbj M@ {ot gjotzvj` jsjv| ?> gle le o gldvm~iopj vjo jv "T|ejvk|

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

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  • 7/31/2019 The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

    20/20

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