RiboSW - an effective tool for searching riboswitches                                                                                                                                              Run webserver   About
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► Introduction

RiboSW is a tool for searching putative riboswitches in a sequence. We characterize each riboswitch as two crucial parts, the RNA secondary structure and the functional region, and RiboSW focuses on these two characteristics to search putative riboswitches. The sequence conservation is only taken into consideration of the functional region, and therefore RiboSW is capable of dealing with the compensatory mutation of the base-paired regions. In addition to web server, we also provide the search program which allows user search locally and describe the new riboswitches for searching.

► Program flow

► Twelve kinds of riboswitches

◇ Purine:  Rfam  RNALogo
Purine riboswitches are RNA structures that regulate protein biosynthesis in response to purines. In general, riboswitches are metabolite-binding domains within certain messenger RNAs that act as precision sensors for their corresponding targets. Allosteric rearrangement of mRNA structure is mediated by ligand binding, and this results in modulation of gene expression. Purine riboswitches are a class of riboswitches that selectively recognises guanine and become saturated at concentrations as low as 5 nM. In Bacillus subtilis, this mRNA motif is located on at least five separate transcriptional units that together encode 17 genes that are mostly involved in purine transport and purine nucleotide synthesis. As some members of this family are also specific for adenine or deoxyguanosine, this family are termed purine riboswitches.

◇ Lysine:  Rfam  RNALogo
The Lysine riboswitch is a metabolite binding RNA element found within certain messenger RNAs that serve as a precision sensor for the amino acid lysine. Allosteric rearrangement of mRNA structure is mediated by ligand binding, and this results in modulation of gene expression. This riboswitches is found in a number of genes involved in lysine metabolism, including lysC. The lysine riboswitch has also been identified independently and called the L box.

◇ FMN:  Rfam  RNALogo
The FMN riboswitch (also known as RFN element) is a highly conserved RNA element that is found frequently in the 5'-untranslated regions of prokaryotic mRNAs that encode for flavin mononucleotide (FMN) biosynthesis and transport proteins. This element is a metabolite-dependent riboswitch that directly binds FMN in the absence of proteins. In Bacillus subtilis, the riboswitch most likely controls gene expression by causing premature transcription termination within the 5' untranslated region of the ribDEAHT operon and precluding access to the ribosome-binding site of ypaA mRNA.

◇ TPP:  Rfam  RNALogo
In molecular biology, the THI element is a highly conserved RNA secondary structure. It serves as a riboswitch that binds directly to thiamine pyrophosphate (TPP) to regulate gene expression through a variety of mechanisms in archaea, bacteria and eukaryotes. TPP is the active form of thiamine (vitamin B1), an essential coenzyme synthesised by coupling of pyrimidine and thiazole moieties in bacteria. The THI element is an extension of a previously detected thiamin-regulatory element, thi box. Analysis of operon structures has identified a large number of new candidate thiamin-regulated genes, mostly transporters, in various prokaryotic organisms.

◇ Glycine:  Rfam  RNALogo
The bacterial glycine riboswitch is an RNA element. Glycine riboswitches usually consist of two metabolite-binding aptamers domains with similar structures in tandem. The aptamers cooperatively bind glycine to regulate the expression of downstream genes. In Bacillus subtilis, this riboswitch is found upstream of the gcvT operon which controls glycine degradation. It is thought that when glycine is in excess it will bind to both aptamers to activate these genes and facilitate glycine degradation.

◇ SAM:  Rfam  RNALogo
The SAM riboswitch (also known as the S-box leader and now also called the SAM-I riboswitch) is found upstream of a number of genes which code for proteins involved in methionine or cysteine biosynthesis in Gram-positive bacteria. Two SAM riboswitches in Bacillus subtilis that were experimentally studied act at the level of transcription termination control. The predicted secondary structure consists of a complex stem-loop region followed by a single stem loop terminator region. An alternative and mutually exclusive form involves bases in the 3' segment of helix 1 with those in the 5' region of helix 5 to form a structure termed the anti-terminator form. However, many SAM riboswitches are likely to regulate gene expression at the level of translation.

◇ Cobalamin:  Rfam  RNALogo
Cobalamin riboswitch also known as B12-element is a cis-regulatory element which is widely distributed in 5' untranslated regions of vitamin B12 (Colbalamin) related genes in bacteria. Riboswitches are metabolite binding domains within certain messenger RNAs (mRNAs) that serve as precision sensors for their corresponding targets. Allosteric rearrangement of mRNA structure is mediated by ligand binding, and this results in modulation of gene expression or translation of mRNA to yield a protein. Cobalamin in the form of adenosylcobalamin (Ado-CBL) is known to repress expression of proteins for vitamin B12 biosynthesis via a post-transcriptional regulatory mechanism that involves direct binding of Ado-CBL to 5' UTRs in relevant genes, preventing ribosome binding and translation of those genes.

◇ yybP-ykoY:  Rfam  RNALogo
The yybP-ykoY leader RNA element was originally discovered in E. coli during a large scale screen and was named SraF. This family was later found to exist upstream of related families of protein genes in many bacteria, including the the yybP and ykoY genes in B. subtilis. The specific functions of these proteins are unknown, but this structured RNA element may be involved in their genetic regulation as a riboswitch.

◇ ykkC-yxkD:  Rfam  RNALogo
The YkkC/YxkD leader is a conserved RNA structure found upstream of the ykkC and yxkD genes in Bacillus subtilis and related genes in other bacteria. The function of this family is unclear although it has been suggested that it may function to switch on efflux pumps and detoxification systems in response to harmful environmental molecules. The Thermoanaerobacter tengcongensis sequence AE013027 overlaps with that of purine riboswitch suggesting that the two riboswitches may work in conjunction to regulate the the upstream gene which codes for TTE0584 (Q8RC62), a member of the permease family.

◇ SAM alpha:  Rfam  RNALogo
The SAM-II riboswitch is a RNA element found predominantly in alpha-proteobacteria that binds S-adenosyl methionine (SAM). Its structure and sequence appear to be unrelated to the SAM riboswitch found in Gram-positive bacteria. This SAM riboswitch is located upstream of the metA and metC genes in Agrobacterium tumefaciens, and other methionine and SAM biosynthesis genes in other alpha-proteobacteria. Like the other SAM riboswitch, it probably functions to turn off expression of these genes in response to elevated SAM levels.

◇ PreQ1:  Rfam  RNALogo
The PreQ1-I riboswitch is a cis-acting element identified in bacteria which regulates expression of genes involved in biosynthesis of the nucleoside queuosine from GTP. This RNA element known as a riboswitch binds preQ1 (pre-queuosine1), an intemediate in the queuosine pathway. Riboswitch function has been characterised in the bacterium Bacillus subtilis, where the riboswitch is located in the leader of the ykvJKLM (queCDEF) operon which encodes four genes necessary for queuosine production. In this organism, PreQ1 binding to the riboswitch aptamer is thought to induce premature transcription termination within the leader to down-regulate expression of these genes. The preQ1 riboswitch is distinguished by its unusually small aptamer, compared to other riboswitches. PreQ1-II riboswitches also bind preQ1, but have an unrelated, distinct structure.

◇ glmS:  Rfam  RNALogo
Glucosamine-6-phosphate activated ribozyme (GlcN6P) is found in the 5'UTR of the mRNA which is coding for GlmS. GlmS is an enzyme that uses fructose-6-phosphate and glutamine to generate glucosamine-6-phosphate. The ribozyme catalyses self cleavage of the glmS mRNA thereby regulating GlmS activity. The GlmS element is only catalytic when bound to glucosamine-6-phosphate. The glucosamine-6-phosphate is a cofactor for the catalytic reaction, directly participating in the chemistry. This is the only known case of a ribozyme using a small-molecule cofactor at present.

Department of Computer Science and Information Engineering, National Central University, Tao-yuan, Taiwan
Contact with site administrator:
Tzu-Hao Chang