NEWSFEATURE NATURE|

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©2006 Nat
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ngGr
oup
 NATURE|
Vo
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1|25 M
ay2006 NEWSFEATURE
IN
.DARK

WHATISAGENE?
C

Th
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‘G
en e’i sno tat ypic alfou r-letter Lauren c eH ur s
ta tth eU ni versityo fB ath ,UK . v iou slyun im a g
in eds c op eofRNA .
w ord. Itisn oto ffen sive. I
ti sn ev e
r “Allo f that inf orm ations eriou slych al
len ges Th eon eg en e
,on ep roteinid eai scom in g
bl eep edou to fTVshow s. And ourcon ven tion ald efinitiono fag en e,”s a s und
y erp articu lara ssau lt fromr esear ch erswh o
wh er eth em e anin go fmo stf ou r
- molecul arb iolo gistB in gR ena t th eU niversit y a recomp reh en sivelye xtra ctin gandan alysin g
letterwo rd si sall tooc le ar
, th ato fg en eisno t
. ofC al
if orni a
,S anD ie go.And th einf orm a
tion th eRNA m e ssa ges,o rt ran script s,m anu fa c
-
Them oree xp erts ci entistsb ec om einm o
l ecu- challen g eisabou ttog e
te ventou gh er.L at er tu redb yg enom es,in c
lud in gth ehum anand
larg en e
ti cs, th ele sse asyi tis tob esu reabou t thisy ea r
,ag luto fd ataw il
lb er eleas edf rom mou s eg enom e.R es ear ch ersl edb yThom as
what,ifan yth in g,ag en ea ctu ally is
. thein te rn ation alEn cyclop ed iao fDNAE le- G in ger asa tth ecomp an yA ffym etri xinS an t a
Ri ckY oun g
,ag en eti cista tth e Wh iteh ead ments(ENCODE )p r oject.Th ep ilotph aseo f C l ara,C al
i forni a
, fore xam ple,r ecen t
l ystud ied
Institu teinC amb rid ge,M assa chu setts,s ays ENCODE in v o
l vess crutin iz
in gr ough ly1%o f a l
lth et r ans cript sf romt ench romo som es
thatwh enh e firsts tar ted t each in ga sayoun g thehum ang enom e inunp rec ed entedd et ai
l; a cro sse igh thum anc elllin esandwo rk edou t
professo rtwod ec ad esa go, ittoo kh imabou t thea imi stof inda llth e pre c
i selywh ereon th ech r o-
tw oh ou rst o teach fre sh-fa cedund e rgradu at
es sequ en ce sth ats erveau s eful “W e’vecometothe mo som ese a cho fth et ran -
whatag en ew asand th enu t sandbo ltso fhow purpo seande xplain wh a
t rea l
iza tiontha tthe scrip tsc am e from 3
.
itwo rk ed.T od ay,h eandh isco ll eagu esn eed thatpu rpo sei s.“Wh en w e Th ep ic tur eth es es tud i es
thr eem onth so fl ectu r est oc on ve yth ec on cept sta
r ted th eENCODEp r o
j ect
genome isfu llo f pain t i s on e of
ofth eg en e,and th at’
sno tb ecau s eth estud en ts Ih ada d ifferen tv iew o f o verlapp ingt ransc rip ts .” m ind -bo g gl
in gcomp l exit y
.
arean yl essb righ t.“ It tak esawho les em ester whatag en ew as,”s a yscon - —Ph ill
ipKap ranov In ste ad o fd is creteg en e
s
tot each th iss tu f
f t ot a
l ent edg r adu ates,”Y oun g tr
ibu tin gr es earch erRod eric dutifu lly m a
ss -p rodu cin g
says.“Itu sed tob ew ecou ldg iveaon e-offd e
f- Guigoa tth eC en terfo rG enom icR e gu lation id en ticalRNAt r an scrip ts
,at eem in gm a ssof
initionandnow it’smu chmo r ecom pl
i cated.” inB a rcelon a.“Th ed egre eo fcomp lexityw e’ve t ran s criptioncon vertsm an ys egm ent so fth e
Inc l as s
i calg en etics,ag en ew asana bstr a
ct seenw asno tan ti c
ip ated.” gen om ein tom u
lti p
l eRNAr i bbon so fd ifferin g
con cep t —aun ito f inh eritan ceth atfer r
i eda len gth s.Th eser ib bon sc anb eg en e rated f r om
cha ract eristicf romp a
r en ttoch ild.A sb io- Und e rfir e boths trand so fDNA ,r ather th an fr om ju ston e
chem istr yc am e int o itsown ,tho sech ar acter- Thefirsto fth ec om p
l exiti
e stoch al
l eng em olec- a sw ascon vention ally thou gh t.Som eo f th ese
ist
i csw erea ss ociat edw ithen zym eso rp r oteins
, ula
rb i olo gy’sp arad igm o fas in gle DNA t ran s criptscom e fr omr egion so fDNAp re vi
-
one fore achg en e.Andw i
th th ead vento fm ol- sequ enc een c odin ga sin g
l ep rot e
inw asa ltern a- ou s
l yid en t
ifieda sho ldin gp rotein - cod in g
ecul arb iolo g y,g en esb e cam er eal
,ph ysical tivesp l
icin g,d isco ver edinv iru sesin1 9 77( see g en es.Bu tm an yd on ot.“ I
t’ssom ewh atr ev olu-
thin gs —s equ en ceso fDNAwh ichwh enc on- ‘H ardt ot ra ck’
,o verle a
f).M o sto fth e DNA t ion a ry
,”s aysG in ge ras’sco lle agu e Ph il
lip
vertedin tos t rand so fso -c a
ll ed m ess en ger seq uenc esd es c
ri b
in gp r o
t e
in sinh um an sh avea K ap rano v
.“W e
’ vecom eto th er eali zat
ion th at
RNAcou ldb eu seda sth eb asisfo rbu ild ing modu lara rr an gem en tinwh i che xon s
,wh ich th eg en om eis fullo fo verla ppin gt ran scrip ts.”
theira sso ci atedp r oteinp i eceb yp i ece.Th e carry the in s
t ruction s form a kin gp rotein s
,a re Oth erstud ies,on eb yGu ig o
’st eam4,andon e
greatco iledDNA mo le cul eso fth ech romo - intersp ersedw ithn on -cod in gin tron s
.Ina lter- b yg en eticistRo t emSo rek5,nowa tT elA viv
som esw er es eena sl on gs trin gsonwh ichg ene nat
i vesp licin g,th ec e
llsn ip sou tint ron sand Un i ver s
it y
,I s rael,andh isco llea gu es,h ave
sequ en c ess atli ked is creteb ead s. sew st o geth erth ee x onsinv ariousd iffer ent h int eda t ther e ason sb ehind th em asso f tran -
Th isp i ctu rei ss tillth ewo rkin g mod e
lfo r orders,c reatin gm ess agesth atc anc od ef ord if
- s crip tion .Th etwot e am sin v est
i gat edo cc a
-
man ys cien tis ts
.Bu ttho s ea tth efo refron to f ferentp r otein s
.O ve rth ey earsg en e
ticistsh ave s ion alr epo rt sth att ran s cr
ip tionc ans ta rta ta
gen et
icr ese archs ee ita sin c reasin glyo ld-fa sh- al
so d o cum en tedo verla ppin gg en es,g en es DNAs equ en c ea sso ci atedw ithon ep rot ein
ion ed —ac rud eapp ro x
im at
ionth at,atb est
, wi
thing en esandc oun t
l e
sso th erw e
i rda rran ge- andruns traigh tth rou ghin toth eg en efo ra
hidesf as cin atin gn ewcomp l exitiesand ,a t ments( see‘M udd lingo verg en es’
,o verleaf )
. comp letelyd iffer en tp ro tein,p rodu cin ga
worst,b l
ind si tsu se rstou sefu ln ewp aths Altern ativesp l
i c
in g,h ow ever,didn otin itself fu sed tran script.B yd elvin g intod at ab as esof
ofenqu ir y
. requir ead ra st
icr eapp rais a
lo fth eno tiono fa hum anRNAt r an scrip ts, Gu igo’st e ame sti-
In form ation ,its e em s
, isp arceledou ta lon g gene;itju stsh ow ed th atsom eDNAs equ en c e
s m ateth at4– 5%o fth eDNAinr e gion scon -
chr omo som esina mu ch mo r ecom ple xw ay couldd es c
ri bemo reth anon ep rot e
in.T od a y
’s v en tion allyr eco gn izeda sg en esis tran s crib ed
thanw aso rigin allysuppo sed .RNAmo l ecu l
es assaulton th eg en econ cep t
i smo refa rre ach - in th isw ay
.P rodu cin g fused tran scrip tscou ld
aren ot ju s
tp assi vec ondu its thr ou ghwh ich th e ing,fu el
l ed largelyb ystud iesth a
tsh ow th ep re- b eon ew a yfo rac e
ll tog en erat eag r eate rv ari-
gen e
’sm ess ag eflow s int oth ew orldbu ta ctive etyo fp ro tein sf romal im itednumb ero f
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at
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Ane ye-op en in gs tud yl a sty e arr aisedth e DNAknownobo rd e rs— th ate achs equ en ce
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tp l an tssom etim esr ew riteth eir re ach esin toth en e xtandb eyond .Th isid ea
DNAon th eb a s
iso fRNAm e ssa gesinh eri
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1
fromg en er ation sp ast .As tud yonp age4 69of fr om th eENCODEp r ojectwh en itsr esu l
t sa r
e
thisissu esu gg eststh atacom par ableph en om - pu blish ed later thisy ear.
enonm i gh to c cu rinm ic e
,andb y im plication Ka pran ovando th er ss ayth a
t the yh a ved o c-
2
ino th e rm amm als .Ifth i st yp eo fph enom e- um en ted m an ye xamp leso ft r an scrip tsin
non isind e edw id esp r ead,i t“w ouldh av ehu ge SpoolsofDNA( abo ve)stil
lh arbou rsurprise s
,w ith whi chp rotein -cod in ge xon sfr omon ep arto f
imp lic ation s,
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teno ver
l apping then e x. t
t heg enom ecom bin ew ithe xon sfr oman oth e
r
399
©2006 Nat
urePubl
ishi
ngGr
oup
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ay2006

partthatc anb ehund redsofthou sandso f whens cien tistsh av ese arch ed for th eg enetic
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©2006 Nat
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oup
 NATURE|
Vo
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ay2006 NEWSFEATURE

on em e answh en the y talka bou tg en esb e ca use

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.,V ictor,J
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Gr
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. 3
. ChengJ .e tal.Scien ce308,1 149 –1154(2005 ).
measurethee xtento f one‘g ene’
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tot zw ant stoe x
am ine R.A.N ature435 ,637 –645(2005 ).
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Netwo rkP rojectCo reG roup)S c
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thanon e,gen e
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llingham ,A .T.e tal.Science309 ,1570 –1573(2005 ).

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