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    RIBOSWITCHESGENETIC CONTROL ELEMENTS

    INTRODUCTION G ! "#$ $%!"&%' # ! !"# ' * " & %* '# #! . " /, $ '' / " & %! "% ! #&%!/ !" ! / !.

    #%$ /#$ ' # ! ' . &.#! ! "#$ & #%! "" &! 5 M% " !%7! / $ !# / %* ! "#$ $%!"&%' #! %' %* &%" #! * $"%& " " ! $ /#$ ' !

    . #$ ' "#/ '# ! " ! /% ' " " ! & #%! . ' $"# '. #!" & $"#! 7#" " DNA8 /RNA R# % 7#"$ # $%#! . D&5 R%! ' B& & #! 2002 7 ! & %&" " " /RNA !$% #! !9./ %*

    #" /#! B1 ! B12 #% .!" # #! E5$%'# $% ' #! %$# " / " %'#" (7#" % " ' & &%" #! ) !" . & RNA $%/ %! !" " " #!" & " '# ! #! #! ! ! & ' "#%! "% & %! "% /%' $ ' ! ' 7#" #! $ '' 5

    Identifying the first riboswitches I" # !%7! " " & #%! %* ! & %! # ' *%& .!" # ! #/ %&" %* $% !9./ B12 #! $" #

    & & 7 ! " ' ' %* " # !"# ' $% !9./ 7 & : " 5 S & ' "" / " 7 & / "% # !"#*. " &%" #! * $"%& & %! # ' *%& ! #! $% !9./ B12 !

    & & #! " ! , !% # !$ %* $ &%" #! 7 *% ! 5 S / # " $ #! %*' #! / # " $%!"&%' *%& #% .!" # %* FMN ! ' % " # /#! .&% % "

    #% .!" # 5 T ! ' #! ' ! $%!"&%' /. " " " 7 & *#& " /#! *%& % # ' % 7#"$ * !$"#%!5

    PROOF OF RIBOSWITCHESF% & '#$ "#%! #! 2002 &% # " # !$ "% $%!*#&/ /. " #! %' #! " $"#%! %* / " %'#"#! #! RNA

    A $%/ #! "#%! %* RNA &% #! ! : #'# / # '. # . $%!*#&/ " " " /% " # '. $%! &%&"#%! %* " ;

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    IN !INE PROBIN" E**#$# !" . &%'. # # % # ' 7 ! RNA # ! "& $" & 7 & RNA $%! "& #! . $%! &.

    "& $" & %& . #! #! "% " '# ! $ !!%"5 T & *%& . &%'. # %$$ & #! ! "& $" & ! '#! & RNA #'. " ! 7#" $%! &. "& $" & %&

    '# ! 5 G ' ' $"&% %& # & '" %* #!'#! &% #!

    L ! 1= !% RNA L ! 2= RNA $ " 7#" R! T1 L ! 3= RNA $ " 7#" L ! 4 > ; = %!" ! % $' #! !$ ! & !$ %* FMN *%& 40 "

    2; OC5 A&&%7 !%" & #%! %* RNA " " $ / ' $ "# ' "% $' #! "

    & !$ %* FMN5

    OCCUR#NCE R# % 7#"$ %$$ & #! $" , " * !$"#%! ' % 7#"$ %* %! ". ( " TPP % 7#"$ ) !

    # $% & #! ' !" ! $ &" #! * ! #5 TPP % 7#"$ ' % ! & #$" #! &$ , " !%"! / !" ''. " " 5 I! 200? " % 7#"$ 7 # $% & #! / ! (#! " 3< !"& ! ' " & #%! %* " /RNA !$% #!

    $ ' & ! %" '# ' &%7" * $"%& (@EGF), &%" #! $"#$ ' *%& '%% ' *%&/ "#%! A "& & %! #RNA 7#"$ & ' " @EGFA & #%! P &" % S &%" # R . "5 ', ( %# 105103 8! " & 0 ;? ))

    STRUCTUREA ". #$ ' /RNA "& ! $ " $%! # " %* " & $"#%!

    1) ;< U!T& ! ' " & #%! (;

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    R# % 7#"$ ! "% *%&/ /%' $ ' & &$ #" $" & 7#" **#$# !" $%/ ' #". "% $ &&.% " "7% / #!* !$"#%!

    15 M%' $ ' & & $% !#"#%! A " / & ! #! ' '# ! ( "& $" & #! #! %$ ", # **#!#"., #$#*#$#".)

    25 R ' "%&. D%/ #! (E & #%! ' "*%&/) $%!"&%' ! & #%! (& $" %! '# ! #! #! . "" / &, $%!*%&/ "#%! ' $ ! '" & ! & #%!)

    $O!ECU!#R RECO"NITION R# % 7#"$ & "& $" & !%!$% #! RNA %/ #! " " ' $"# '. #! / " %'#" ! $%!"&%' !

    & #%! (M ! ' ! B& & 2004 C% #! " '5 200 R%" ! B& & 200?)

    CONFOR$#TION#! CH#N"ES #!TER "ENE E%PRESSION W ! / " %'#" # !%" % ! (-M), " & #%! ' "*%&/ #!$%& %& " " 7#"$ #! : !$ #!"% !

    !"#-" &/#! "%& " / '%% (AT), ! " "& ! $ "#%! &%$ " &% " $% #! & #%! %* " /RNA5 W ! / " %'#" #! (+M), " 7#"$ #! : !$ # #!$%& %& " #!"% " " / & %/ #!, ! "

    & #%! ' "*%&/ *%' #!"% " &/#! "%& " /-'%% (T), $ #! "& ! $ "#%! "% %&"5

    RE"U!#TION R# % 7#"$ & ' " & ' / " %'#$ " 7 . B#% .!" # %* #" /#! ( 5 5 %*' #!, " # /#! !

    $% ' /#! > M " %'# / %* / " #%!#! , '. #! ! ! 5 R# % 7#"$ & ' " " "& ! $ "#%! #!#"# "#%!, % " "& ! $ "#%! ' & ' "#%!, "& ! ' "#%! #!#"# "#%!, !

    ". %* %" & * !$"#%! 5 R $ !"'. CRISPR RNA ($' " & & ' &'. #!" & $ %&" '#! &%/#$ & " ) ! %7! "%

    *%&/ #$ "# #// ! . " / %* $" ' $ '' . #!" &* ! 7#" ' /# ! #!* $"#%! 5

    RIBOSWITCH

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    RIBOSWITCHES IN P!#NTS $ET#BO!ITE $EDI#TED CONTRO! OF SP!ICIN"#ND #!TERN#TI&E '( END PROCESSIN" OF )RN# TR#NSCRIPTS*

    M " %'#" / # " $%!"&%' %* '#$#! ! '" &! "# 3< ! &%$ #! %* mRNA "& ! $ " 5

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    RIBOSWITCHES IN Neurospora crossa

    RIBOSWITCHES IN PRO+#R,OTES

    I!!USTR#TION OF #PT#-,$E B#SED RIBOSWITCH SENSOR

    M " %'#" / # " $%!"&%' %* '#$#! ! '" &! "# 3< ! &%$ #! %* /RNA "& ! $ " 5 W ! TPP$%!$ !"& "#%! & '%7 (' *"), %&"#%! %* " / P4 ! P; #!" & $" 7#" " ;< '#$ #" ! " & . & !" '#$#! 5T "& ! $ " &%$ #! #" '%$ " "7 ! " ;< '#$ #" ! " TPP " / & # & " #! , ! #" & '" #!*%&/ "#%! %* "& ! $ " 7#" %&" 3< UTR " " &/#" # & #%!5 I! " & !$ %* ' " TPP

    $%!$ !"& "#%! ( "), TPP #! "% " " / & $%"& ! $ "#%! ''., 7 #$ ' "% "& $" & ' $ ! " " & !"#!" & $"#%! 7#" " ;< '#$ #" 5 S '#$#! %$$ & ! & /% " "& ! $ " &%$ #! #" 5 T& ! $ "#%! $%!"#!! '" &! "# &%$ #! #" #! " " ! 3< UTR # "% (" # /#! #% .!" "#$ ! THIC) THIC ". IIIRNA 5 T '%! 3< UTR ' "% #!$& RNA " &!% &, $ #! & $ & #%! %* THIC

    6S RNA " "& $" & %* 6S RNA # # '.

    $%! & /%! $" ! 7 . %" #9"% . *%& RNAP #! #! #" & / ' DNA % ! &%/%" &5

    T& ! $ "#%! %* 6S RNA- ! !" ! . "% #! RNAP ( %! !"# ' ) #

    #! # #" . ' & /% !" %* 6S RNA ! &! " !" '#/#" "#%! ( " "#%! &. )5 U %!& '. 7#" ! " !" (% " &%7" ), RNAP #& ' . " .!" # %* %&" "& ! $ "( RNA)5

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    I'' "& "#%! %* ! " 9./ % 7#"$ ! %&5 T / ' " DNA !$% #! & %&" & ! (% ! &' $#* & %& " ' $"% # ) #!$' " / '%% ( & .), ! !"# RBS : !$ (B' ), ! " 9./ (P#! ) ! !RBS : !$ (R B &) #! " # %& & #! " ;< !"& ! ' " & #%! ! & " T &%/%" & ( & !)5 W ! "& ! $ #!" # " / ' " #! $ '' *& &% &.%" "& ! ' "#%! . " / #!$' #! T RNA %'./ & , !"# RBS . #9 "% "RBS "% & !" " % %/ *%&/ #! #! "% #"(OFF)5 I! " & !$ %* $%* $"%& *%& " " 9./ , " $%* $"%! $ '* $' %* " " 9./ "% $"# " & #%! %* " & %&" & ! (ON)

    RIBOSWITCH #CTIN" #S # RIBO-,$E S" # #! B5 "#'# 5 '/ ! $% *%& " !9./ ' " /#! *& $"% -6- % " /# % "& ! * & 5 E!9./ #! $ $%!*%&/ "#%! ' $ ! #! " ' & : !$ ! $"# " %9./ C' %* " ' & & #%! %$$ & 24; ! $' %"# "& / %* " AUG $% %! L "% & $ & #%! C' ! !$ . 1000 *%' #! " & !$ %* G'$N6P5 T B5 "#'# '/S % 7#"$ # $%! & "& / %* " '/S ! 5 D ! $%! #"#%! %* $

    G'$N6P, " '/S ;< UTR # "#/ ' " "% '* $' " $#*#$ #" " #" ;< ! 5 C' ' "%'/S & & #%! " &% ! ! !%7! / $ !# /5

    C#TE"ORI-#TION OF RIBOSWITCHES

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    Riboswitch finder ! '.9 : !$ #! 7 #!" &* $ ! " ! $ $ $#*#$ : !$ ' / !"! $%! &. "& $" & $ '$ ' " ! # ' . " ! & . *%' #! %* " RNA "& $" & 5

    (7775 #%9 !"& /5 !#7 &9 & 5 8 #%#!*%&/ "# 8 % 7#"$ 8 5) RibE. /Riboswitch E.01orer23 &$ !. : !$ *%& !%7! % 7#$ ! *%& %" & & #$"

    %! 5 ( 7775# "5 ! /5/ 8 #%$%/ "%8 5 "/' 5) C$finder /Co45ri5nce )ode1 b5sed RN# )otif finding 51gorith)23 " # "%%' &*%&/ 7 '' %!

    ! '# ! : !$ ! ' % 7 ! " /%"#* # %!'. & !" #! " %* : !$ 5 U *%& /%"#*

    &$ , "& $" & & #$ "#%! $%/ #! *%' #! ! & . ! : !$ $%- "#%!5( "" 887#! ' 5$ 57 #! "%!5 8 " #!- % "8 !& "$" 8CM*#! &W 8CM*#! &I! "5 ' 5)

    RiboSW "%%' *%& &$ #! " "# % 7#"$ #! : !$ 5 T "%%' "7% &" , " RNA$%! &. "& $" & ! * !$"#%! ' & #%! "% &$ " "# % 7#"$ 5 "" 88 % 75/ $5!$" 5 5"78 5

    RIBOSWITCHES #RE #NCIENT RNA !9./ 7 % % #! '/% " & '. & " " %* &%" #! 5 RNA &%" #! $%/ ' " "

    .!" #9 '' !$% &%" #! $ & ! RNA !9./ " #" "# .'-"& ! * & $%& 5 C &" #!'. " & !$ %* % 7#"$ '# "& $" & 7% ' ! !$ " **#$# !$. %* / " %'#$

    &%$ #! %& !# / %* " RNA 7%&' 5 O #% '. " *#& " % 7#"$ 7% ' !%" ! $%!"&%''#! " & #%! %* &%" #! !9./ , "

    " . 7% ' $%!"&%'' " &% $"#%!, &%$ #! ! $"# #". %* " #& %9./ $% !" & &" 5 T & # % # #'#". " " " % 7#"$ # $% & & $'% & ' "# %* RNA 7%&' / " %'#" ! %& 5

    T # $% ' * $" " " $ '' ! "% ! " $%!$ !"& "#%! %* #/ %&" !" $%/ % ! ! " " RNA ! $ % ! *%& " # " 5

    E$ER"IN" #PP!IC#TIONS OF RIBOSWITCHES15 R# % 7#"$ "%%' *%& & ' " ! & #%!525 S" .#! /#$&% # ' ! "#$ 535 R# % 7#"$ !"#/#$&% # ' " & " 545 R# % 7#"$ - $%!"&%' %* $" ' #% &5

    RIBOSWITCHES #S TOO!S FOR RE"U!#TED "ENE E%PRESSION L# ! #! $# ' & #%! . " / & #/ %&" !" ! "#$ "%%' #! !. $%//%! ' %& "%&.5 I! $ & ( $ IPTG) & "%% ! # "% * ' %! #! " ' $ ' 5 N " & ' % 7#"$ " " &

    $"# " . /#!% $# / . " & *%& & & !" ! **%& ' '" &! "# *%& $ '#$ "#%! 5 T ! / '.$#! % 7#"$ *%&/ B5 "#'# 7 *%& '.$#! #! $# ' &% $"#%! %* B "

    ' $"% # 7 #$ &% # %!'. 6 *%' #! $"#%! 7 ! '.$#! 7 5

    STUD,IN" $ICROBI#! "ENETICS L# ! ! #"# % 7#"$ & * ' #! &% $"#%! %* $%! #"#%! ' . &/%& #$ / " !" , &"#$ &'. #!

    $ 7 & ! '' / " !" & ' " '5 E / ' " % .''#! ! #"# .!" "#$ % 7#"$ 7 # ! "% & ' " ! !"# ' ! " "

    /% ' " /%"#'#". ($ &A)5 T $& "#%! %* $ &A-' $ * #%! " " # $ &%/% %/ ' % #"#%! *# " " & #%! ' ' 7 & '%7 #!

    !$ %* " % .''#! " &% $ 7#' ". & #%! ' ' #! " & !$ %* " % .''#! 5 T $ '' 7 & !%!-/%"#' #! !$ %* #! $ & " & #! " #& /%"#'#". #! & !$ %* " % .''#! 5

    T # / !" %7 " " $ &A # ! "# & ' "%& %* "% & "#%! #! E5$%'#5RIBOSWITCHES #S #NTI $ICROBI#! T#R"ETS

    R# % 7#"$ $% ' " & " *%& !% ' !"# #%"#$ 5 I! , %/ !"# #%"#$ 7 % / $ !# / %* $"#%!7 ! !%7! *%& $ ! %7! "% % & " . " & "#! % 7#"$ 5

    http://www.biozentrum.uniwuerzburg.de/bioinformatik/riboswitch/http://www.biozentrum.uniwuerzburg.de/bioinformatik/riboswitch/http://www.ibt.unam.mx/biocomputo/ribex.htmlhttp://wingless.cs.washington.edu/htbin-post/unrestricted/CMfinderWeb/CMfinderInput.plhttp://wingless.cs.washington.edu/htbin-post/unrestricted/CMfinderWeb/CMfinderInput.plhttp://ribosw.mbc.nctu.edu.tw/http://www.biozentrum.uniwuerzburg.de/bioinformatik/riboswitch/http://www.ibt.unam.mx/biocomputo/ribex.htmlhttp://wingless.cs.washington.edu/htbin-post/unrestricted/CMfinderWeb/CMfinderInput.plhttp://ribosw.mbc.nctu.edu.tw/
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    E P." # /#! !" & $ '', #" # / " %'# #!"% ." # /#! .&% % " 5 P." # /#! .&% % " !%7! "% #! ! $"# " " TPP % 7#"$ , $ #! " $ '' "% $ " .!" # ! #/ %&" %* TPP5 B $." # /#! .&% % " % !%" "#" " *%& TPP $% !9./ , " $ '' # 5

    RIBOSWITCHES B#SED CONTRO! OF B#CTERI#! BEH#&IOR B $" ' $ /%" # ! " # " ! # '. ! 7 '' ! & "%% " ! "#$ ' '5 T #'#". "% /% ' " $" ' /%"#'#". #! & %! "% & #"& &. $ /#$ ' # ! ' 7% ' &% # ! 7

    "%%' *%& #%& / # "#%! ! & '# &. E / ' c e! $ /%" # # ! '#! &%" #! # & &% & // ! ' $ ! & " $%!"&%' %*

    " % .''#! ! #"# 7#"$ 5 R &% & // $ '' 7% ' " ! /# & " & # !" %* " # '# ! !"%!%/% '. '%$ '#9 "% & #%! %* # " % .''#! $%!$ !"& "#%!, 7 #$ # #% & " " $ !!%" $$%/ '# . ! " & ' E5C%'# $ /%" # 5

    PROSPECTS R# % 7#"$ $% ' " & " *%& !% ' !"# #%"#$ 5 I! , %/ !"# #%"#$ 7 % / $ !# / %* $"#%! 7

    ! !%7! *%& $ ! %7! "% % & " . " & "#! % 7#"$ 5 E P." # /#! !" & $ '', #" # / " %'# #!"% ." # /#! .&% % " 5 P." # /#! .&% % "

    ! %7! "% #! ! $"# " " TPP % 7#"$ , $ #! " $ '' "% $ " .!" # ! #/ %&" %*TPP5 B $ ." # /#! .&% % " % !%" "#" " *%& TPP $% !9./ , " $ '' # 5

    R# % 7#"$ $ ! '# "% #% ! %& , / " %'#$ ! #! ! %* %& !# / ! #! ! " & ."& "/ !" 5

    I" %7! " %" !"# ' "% $" & " & " #! " % $" ' # 5 R# % 7#"$ " &! %! !%** ! #! %! " C%!$ !"& "#%! %* " '# ! 5

    A!"# $" ' "& " . 7% ' "% # ! / " %'#" /#/#$ " " #! %! % 7#"$ & $ "%&, " %**& #%! %* " %#!#! ! , ! " & " $ '' %* #/ %&" !" / " %'#" ! & "#! ! '% %* "

    '# ! " " #! "% % 7#"$ ! & ' " . / " %'#$ " 7 . / . $%/ ! 7 &% $ *%&'% #! !"#/#$&% # ' !" 5

    "#%!15 W " & R# % 7#"$ W" % " "& $" & ! & ' "#%! %* R# % 7#"$25 W" % " " $' #*#$ "#%! %* R# % 7#"$ W " & " / & #! '#$ "#%! %* R# % 7#"$