Annotated Bib

mRNA secondary structure

Kudla, G., Murray, A. W., Tollervey, D., & Plotkin, J. . !"##$%. &odin'(se)uence determinants o*
'ene e+,ression in -sc.eric.ia coli. /cience, 0"1!2$"1%, "22("23.
Looked at codon bias in several versions of GFP in E. Coli. Found no significant correlation between
CAI and fluorescene, suggesting that codon adatation was not the rate li!iting ste in endogenous
e"ression. #owever, when a $%& was inserted ustrea! of A$G that had little'no secondar( !&)A
structure, e"ression was unifor!l( increased. T.is su''ests t.at ,ast a certain ,oint, increasin'
codon o,timi4ation reac.es diminis.in' returns i* 25 6TR secondary structure is not similarly
o,timi4ed. *udla et. al. Further h(othesi+e that CAI is not a cause of high e"ression, but rather that
high e"ression causes oti!i+ed CAI. %his was confusing to !e, but the re!ise of the argu!ent as I
understand it is that translation initiation is sole regulator of ost transcritional regulation in the
riboso!e, and that CAI either serves to reduce cell energ( costs ,b( fewer se-uestered riboso!es or
fewer !isfolded roteins.
oru7eni, A. -., &.annarasa,,a, A. /., & /alis, 8. M. !"#90%. Translation rate is controlled :y
cou,led trade(o**s :et;een site accessi:ility, selective RNA un*oldin' and slidin' at u,stream
stand:y sites. Nucleic acids researc., 'kt990$.
E"tre!el( detailed aer looking into secondar( strucutre in the /0 $%& and how this affects gene
e"ression. 1a2or findings include that secondar( structure inhibits !&)A loading onto the 34s
subunit while surrounding linear !&)A ro!otes this loading. $nwinding of this secondar( structure
can i!rove riboso!e loading but re-uires inut of free energ(. 1oreover, standb( site regulates
e"ression indeendentl( of $%& length. Finall(, the stand(b( site reresents a significant target for
gene regulation via cis or trans acting factors ,ste!5loo structures, !i&)A, etc... *e( takeawa(6
/econdary structure in 25 6TR is a ,rimary *actor in determinin' level o* 'ene e+,ression :y
controllin' translation initiation.
7uestion6 Is secondar( structure &E7$I&E8 for a standb( structure to be able to load onto a
riboso!e9
Need to *ind< In one aer, the( assert that secondar( structure in the coding region is less i!ortant to
avoid because riboso!e has G%P owering it so it 2ust trucks through the!.
&odon ias
=ian, W., >an', J. R., Pearson, N. M., Maclean, &., & ?.an', J. !"#9"%. alanced codon usa'e
o,timi4es eukaryotic translational e**iciency. P@o/ 'enetics, 3!0%, e9##"A#0.
7ian et al take a cell wide sa!le of nucleotides associated with riboso!e. %he assu!tion !ade is
that the ti!e it takes for a t&)A to find its codon is inversel( roortional to the fre-uenc( of that
codon in the riboso!e. For e"a!le, a codon that takes a long ti!e to associate with its resective
t&)A should be found associated in the riboso!e site !ore fre-uentl( than one that finds it -uickl(.
%he results show that there is no significant difference in the fre-uencies of biased codons in the
binding site, suggesting that these codon biases do not ro!ote faster translation. %his further suorts
the other generall( acceted osition that codon bias is selected for due to !ore accurate translation.
7uestions6
#ow is this reconciled with t&)A concentration. :houldn0t t&)A0s that have a higher
c(tolas!ic concentration locate their resective codon !ore -uickl(9
Welc., M., Govindara7an, /., Ness, J. -., Billalo:os, A., Gurney, A., Mins.ull, J., & Gusta*sson,
&. !"##$%. Desi'n ,arameters to control synt.etic 'ene e+,ression in -sc.eric.ia coli. Plo/ one,
1!$%, eC##".
!Need to read more closely and ;rite more%
%his aer shows a rational design aroach to gene design, and investigates the role of s(non(!ous
codon bias on e"ression of 8)A Pol and :ingle chain antibod( in E. coli. Contradictar( to Plotikin
,;44<., =elch and colleagues rovide evidence that s(non(!ous codon bias is the result of variation in
e"ression of various for!s of their genes.
#owever, a co!ro!ise is found in so!e of the data, where a >highl( deleterious /0 region was found
to drasticall( decrease e"ression desite good codon bias. T.is su''ests t.at :ot. translation
initiaion and elon'ation can :e rate limitin', and deending on the se-uence, either can be the
li!iting ste in gene e"ression. In Plot
7uestion6 Could it be ossible to anal(+e se-uences fro! Plotkins aer vs =elch aer and deter!ine
if there were di**erent limitin' ste,s in the two studies that lead to the two different conclusions.
@i, G. W., D., -., & Weissman, J. /. !"#9"%. T.e anti(/.ine(Dal'arno se)uence drives
translational ,ausin' and codon c.oice in :acteria. Nature, 131!C0$2%, 203(219.
@iu, ., & =ian, /. . !"#91%. Translational re,ro'rammin' in cellular stress res,onse. Wiley
Enterdisci,linary Revie;s< RNA, 2!0%, 0#9(0#2.
8escribes !echanis!s b( which translation can be altered under stress conditions. &eview describes
how in one stud( it was found that the t&)A concentration of a !eth(lated leucine t&)A increased.
?ther interesting aers
Wald, N., Alroy, M., ot4man, M., & Mar'alit, 8. !"#9"%. &odon usa'e :ias in ,rokaryotic
,yrimidine(endin' codons is associated ;it. t.e de'eneracy o* t.e encoded amino acids. Nucleic
acids researc., 1#!92%, C#C1(C#30.
&.an &T, Pan' >@, Den' W, a:u ER, Dyavaia.
M, e'ley TJ, Dedon P&. Re,ro'rammin' o* tRNA
modi*ications controls t.e o+idative stress res,onse :y
codon(:iased translation o* ,roteins.
Nat &ommun
"#9", 0<$0C.
&odon &onte+t
&annaro44i, G., /c.raudol,., N. N., Faty, M., von Ro.r, P., Fri:er', M. T., Rot., A. &., ... &
arral, >. !"#9#%. A role *or codon order in translation dynamics. &ell, 919!"%, 022(0AC.
%his stud( investigates the role of codon order in gene e"ression. %he( h(othesi+e that reetition of
secific codons that have s(non(!ous counterarts for a single a!ino acid increases translation seed.
$sing several s(nthesi+ed versions of GFP, the( do *ind t.at codon reuse results in si'ni*icantly
im,roved 'ene e+,ression.
%here are several ossible e"lanations for this heno!enon, but the !ost lausible can be e"lained
b( the fact that riboso!e elongation is significantl( !ore raid than the rate of t&)A diffusion awa(
fro! the riboso!e. In addition, t&)As are recharged
7uestions6 Is this !ore i!ortant than codon bias9 /.ould o,timi4er ,ro'rams try to resolve t.is
,ro:lem and sacri*ice codon :ias or vice versa9
Novoa, -. M., & Ri:as de Pou,lana, @. !"#9"%. /,eedin' ;it. control< codon usa'e, tRNAs, and
ri:osomes. Trends in Genetics, "3!99%, 2C1(239.
Aweso!e review article that looks at the !an( deter!inants of gene e"ression. )ot 2ust about codon
conte"t, but has so!e i!ortant takeawa(s. -+,ression o* di**erent 'ene sets can :e re'ulated :y
tRNA modi*ciations. %his is of significance to us because choosing a reference set !ust be done
aroriatel( to reflect the actual e"eri!ental conditions. Preferred codons is not an absolute ter!,
since this can change due to environ!ental factors, and !ore directl(, t&)A !odifications. %herefore,
a codon bias should be defined with reference to the conditions ,#ighl( e"ressed in oti!al
conditions, highl( e"ressed in stress conditions, etc...
&odon 6sa'e and /election on Proteins