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1、Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Riboswitch,Regulation of,Gene Expression,Riboswitches,are present in,untranslated,regions of mRNAs.Their purpose is to regulate gene expression in response to binding small molecule

2、metabolites.,Riboswitches,are defined by two main criteria:,Direct(protein-free)binding of metabolite to RNA,Metabolite-dependent regulation of genes,This movie demonstrates the molecular events common to most bacterial,riboswitches,.Resources are listed at the end of the movie.,Part I:,Gene Regulat

3、ion by a,Typical,Riboswitch,Bacterial,riboswitches,are present in the,5,untranslated,region of mRNAs.,Transcription is regulated by the gene promoter and transcription initiation factors,RNA polymerase initiates transcription.,The RNA folds,intramolecularly,in local regions of,complementarity,presum

4、ably,while transcription is proceeding.,A long,untranslated,leader is produced first.,Nascent RNA,RNA,polymerase,DNA template,RNA,polymerase,Case 1:,Cellular concentration of metabolite is too low to occupy the,riboswitch,binding site.,Transcription and,3,4,2,1,RNA,polymerase,U,U,U,U,U,A,U,G,RNA,pol

5、ymerase,Case 1:,Cellular concentration of metabolite is too low to occupy the,riboswitch,binding site.,Transcription and,intramolecular,RNA folding continue.,3,4,2,1,3,4,2,1,U,U,U,U,U,A,U,G,Case 1:,Cellular concentration of metabolite is too low to occupy the,riboswitch,binding site.,Translation is

6、initiated.,Ribosome,Typically the new mRNA codes for a biosynthetic or transport protein that raises the intracellular level of the metabolite.,Gene regulation,(next case)is accomplished by variations in the interactions of the regions highlighted in,orange,.,Transcription and,intramolecular,RNA fol

7、ding continue.,3,4,2,1,Case 2:,Cellular concentration of metabolite,(X),is high.,Intramolecular,folding can lead to an alternate conformation.,RNA polymerase produces the long,untranslated,leader region.,The alternate,riboswitch,conformation is stable when metabolite is bound.,X,X,X,X,X,RNA,polymera

8、se,X,Nascent RNA,DNA template,Case 2:,Cellular concentration of metabolite,(X),is high.,Intramolecular,folding can lead to an alternate conformation.,RNA polymerase produces the long,untranslated,leader region.,The alternate,riboswitch,conformation is stable when metabolite is bound.,X,X,X,X,X,X,Tra

9、nscription continues.,U,U,U,U,U,RNA,polymerase,3,4,2,1,Case 2:,Cellular concentration of metabolite,(X),is high.,X,X,X,X,X,Transcription continues.,RNA,polymerase,Now,RNA folding leads to formation of an intrinsic terminator.,U,U,U,U,U,X,X,3,4,2,1,3,4,2,1,Case 2:,Cellular concentration of metabolite

10、,(X),is high.,X,X,X,X,X,Transcription continues.,RNA,polymerase,Now,RNA folding leads to formation of an intrinsic terminator.,U,U,U,U,U,X,The transcript is never completed and the metabolite biosynthetic or transport protein is not produced.,3,4,2,1,Review,Case 1:,Metabolite is limited.,Case 2:,Met

11、abolite is abundant.,U,U,U,U,U,X,U,U,U,U,U,A,U,G,ORF,Transcription is completed.,Biosynthetic and/or transport proteins are expressed.,Transcription is terminated.,Proteins are,downregulated,.,X,X,X,X,3,4,2,1,3,4,2,1,Part II:,The Expanding Universe,of,Riboswitches,an expression platform for gene reg

12、ulation.,A metabolite-binding,aptamer,domain,and,Riboswitch,Functions,U,U,U,U,U,X,3,4,2,1,Riboswitches,were defined earlier by two main criteria:,Direct(protein-free)binding of metabolite to RNA,Metabolite-dependent regulation of genes,These two activities are accomplished by two functionally separa

13、te domains on the RNA:,an expression platform for gene regulation.,A metabolite-binding,aptamer,domain,and,Riboswitch,Functions,U,U,U,U,U,X,3,4,2,1,Direct(protein-free)binding of metabolite to RNA,Metabolite-dependent regulation of genes,These two activities are accomplished by two functionally sepa

14、rate domains on the RNA:,Because of the modular nature of RNA structures,different types of expression platform can be linked to the conserved,aptamer,domain.,This leads to variations in,riboswitch,mechanism,Riboswitch,Mechanisms,This movie showed the most common case for bacterial,riboswitches,:,Li

15、gand,binding leads to,transcription termination,and,reduced,gene expression.,U,U,U,U,U,X,5,ORF,X,Riboswitch,Mechanisms,Riboswitches,also regulate translation and anti-termination,Ligand,binding leads to,transcription termination,and,reduced,gene expression.,U,U,U,U,U,X,5,ORF,Ligand,binding sequester

16、s,the,Shine-,Dalgarno,sequence and reduces gene expression.,Ligand,binding leads to,antiterminator,formation and,increased,gene expression.,U,U,U,U,U,X,5,A,U,G,ORF,X,X,X,5,A,U,G,ORF,AGGAGG,X,Riboswitch,Mechanisms,They also affect RNA integrity,and perhaps splicing and stability.,Ligand,binding leads to,mRNA cleavage,by a new,natural,ribozyme,.,X,5,Ligand,binding could control,splicing,in,eukayotes,.,Possibly,ligand,binding to the 3,untranslated,region could affect,mRNA stability.,A,U,G,ORF,X,5,A