Summary

Note on Riboswitches

This Rfam family TPP (RF00059) represents an aptamer domain of a full riboswitch TPP riboswitch aptamer (THI element). Riboswitches are non-coding RNA structures that regulate gene expression in response to ligand. Each riboswitch has two main parts: the aptamer domain and the expression platform. The aptamer domain is highly conserved to precisely bind its ligand. However, the expression platform has multiple modes of gene regulation, which introduces sequence and structure variability that increases difficulty in its detection through covariance model searching. For more information see the original publications.

Wikipedia annotation Edit Wikipedia article

The Rfam group coordinates the annotation of Rfam families in Wikipedia. This family is described by a Wikipedia entry TPP riboswitch. More...

The Wikipedia text that you see displayed on our web site was retrieved from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button above ("Edit wikipedia entry") takes you to the edit page for the article directly within Wikipedia.

Before you edit for the first time

Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.

You should take a few minutes to view the following pages:

Things you should know

How your contribution will be recorded

Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia entry" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer’s IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.

If you have problems editing a particular page, contact us at rfam-help@ebi.ac.uk and we will try to help.

Information we would like to see added

We would value contributions that are referenced directly to the primary literature. Information on structure and function will be especially valuable.

Adding references is explained by this Wikipedia how-to article.

For a good example of what is possible in wikipedia, look at the Hammerhead Ribozyme entry.

Does Rfam agree with the content of the Wikipedia entry ?

Rfam has chosen to create Wikipedia entries for all of our RNA families and to open them up to community annotation. While the original Wikipedia article that we import was (in most cases) generated from Rfam annotations, the Wikipedia article you see now may bear little resemblance to that original text. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Rfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.

Contact us

If you have problems editing or experience problems with these pages please contact us.

If you are interested in contributing to a wide range of articles relating to RNA, see the Wikiproject RNA page.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

Sequences

Alignment

There are various ways to view or download the seed alignments that we store. You can use a sequence viewer to look at them, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

You can view Rfam seed alignments in your browser in various ways. Choose the viewer that you want to use and click the "View" button to show the alignment in a pop-up window.

Formatting options

You can view or download Rfam seed alignments in several formats. Check either the "download" button, to save the formatted alignment, or "view", to see it in your browser window, and click "Generate".

Download

Download a gzip-compressed, Stockholm-format file containing the seed alignment for this family. You may find RALEE useful when viewing sequence alignments.

Submit a new alignment

We're happy receive updated seed alignments for new or existing families. Submit your new alignment and we'll take a look.

Secondary structure

This section shows a variety of different secondary structure representations for this family. More...

In this page you can view static images showing the secondary structure of this family using a variety of colouring schemes:

Conservation (cons): this plot colours each character by how well conserved it is. A site with 100% sequence conservation is coloured red, 0% is violet.

Covariation (cov): this plot colours each base-pair according to how much the corresponding nucleotides are co-varying. A base-pair position at which every pair of nucleotides is co-variant with respect to every other pair in the alignment gets a score of 2 and is coloured red. Conversely, a base-pair position at every pair is anti-co-variant with respect to every other pair (e.g. lots of mutations to non-canonical pairs) gets a score of -2 and is coloured violet. Further information on this metric can be found in this document.

Sequence entropy (ent): this plot colours each character by how under- or over-represented the residues at the site are. Sites where one or more nucleotides are over-represented while the other nucleotides are either non-existent or near the background frequencies, receive positive scores; sites where all the nucleotides are under-represented receive negative scores. Further information on this metric can be found in this document.

Fraction of canonical basepairs (fcbp): this plot colours each base-pair by the percentage of canonical basepairs (A:U, C:G, G:U) which are found in the corresponding position in the alignment. A pair of sites with 100% canonical pairs is coloured red, a site with 0% is violet.

Maximum parse of the covariance model (maxcm): this plot takes the covariance model for the family and generates the sequence with the maximum possible score for that model. Each character is coloured by how many bits it contributes to the total score.

Sequence: for most of the above cases, the representative sequence used for the backbone is the most informative sequence (MIS). Any residue that has a higher frequency than than the background frequency is projected into the IUPAC redundancy codes.

Normal: this plot simply colours each stem loop

R-chie (rchie): arc diagrams showing secondary structure, calculated using the R-chie package. The consensus secondary structure is visualized as arc diagrams on top of each diagram, where a basepair in an arc, connect two columns of the block of sequences below. The block of sequences below represent the multiple sequence alignment of the Rfam seed, where each sequence is a horizontal strip. Sequences in the alignments are ordered so sequences that best fit the structure are on top, and those that do not fit as well are towards the bottom. For seed alignments for over 500 sequences, 500 random sequences were chosen. Rfam entries without sturcture have a blank plot. Colour information can be found on the R-chie FAQ.

You can also view the secondary structure in the VARNA applet. The applet is shown in a separate pop-up window.

Acknowledgements

The bulk of the code for generating these graphics was kindly supplied by Andreas Gruber and Ivo Hofacker. The statistics were implemented by Rfam.

The VARNA applet is developed by Yann Ponty et al:

VARNA: Interactive drawing and editing of the RNA secondary structure: Kévin Darty, Alain Denise and Yann Ponty Bioinformatics (2009) 25:1974-1975

The R-chie arc diagrams were calculated using R-chie:

R-chie: a web server and R package for visualizing RNA secondary structures: Daniel Lai, Jeff R. Proctor, Jing Yun A. Zhu, and Irmtraud M. Meyer Nucleic Acids Research (2012) first published online March 19, 2012

You can view the secondary structure of the family using the VARNA applet. You can see more information about VARNA iself here.

Species distribution

Sunburst
Tree

Sunburst controls

Hide

Weight segments by...

number of sequences
number of species

Change the size of the sunburst

Small

Large

Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Click on a node to select that node and its sub-tree.

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Tree controls

Hide

The tree shows the occurrence of this RNA across different species. More...

Species trees

For the majority of our families we provide an interactive tree representation, which allows you to select specific nodes in the tree and view the selected sequences as an alignment.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the sequence regions (RNA annotations) in a full alignment, we count the total number that are found in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each RNA is found, which is shown in green. Note that an RNA annotation may appear multiple times on the same sequence, leading to the difference between these two numbers (think of repeats like tRNA where the same RNA is found in tandem along a single sequence).

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the RNA is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree. In these few cases if you do really need to see a representation of the tree for this entry, please contact us and we will be happy to discuss ways to generate it for you.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Trees

This page displays the predicted phylogenetic tree for the alignment. More...

Note: You can also download the data file for the seed tree.

Structures

For those sequences which have a structure in the Protein DataBank, we generate a mapping between EMBL, PDB and Rfam coordinate systems. The table below shows the structures on which the TPP family has been found.

Loading structure mapping...

References

This section shows the database cross-references that we have for this Rfam family.

Literature references

Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS J Biol Chem 2002;277:48949-48959. Comparative genomics of thiamin biosynthesis in procaryotes. New genes and regulatory mechanisms. PUBMED:12376536
Miranda-Rios J, Navarro M, Soberon M Proc Natl Acad Sci U S A 2001;98:9736-9741. A conserved RNA structure (thi box) is involved in regulation of thiamin biosynthetic gene expression in bacteria. PUBMED:11470904
Winkler W, Nahvi A, Breaker RR Nature 2002;419:952-956. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. PUBMED:12410317
Sudarsan N, Barrick JE, Breaker RR RNA 2003;9:644-647. Metabolite-binding RNA domains are present in the genes of eukaryotes. PUBMED:12756322
Kubodera T, Watanabe M, Yoshiuchi K, Yamashita N, Nishimura A, Nakai S, Gomi K, Hanamoto H FEBS Lett 2003;555:516-520. Thiamine-regulated gene expression of Aspergillus oryzae thiA requires splicing of the intron containing a riboswitch-like domain in the 5'-UTR. PUBMED:14675766
Serganov A, Polonskaia A, Phan AT, Breaker RR, Patel DJ Nature. 2006;441:1167-1171. Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch. PUBMED:16728979
Welz R, Breaker RR RNA. 2007;13:573-582. Ligand binding and gene control characteristics of tandem riboswitches in Bacillus anthracis. PUBMED:17307816
Lee K, Huang X, Yang C, Lee D, Ho V, Nobuta K, Fan JB, Wang K PLoS One. 2013;8:e70720. A genome-wide survey of highly expressed non-coding RNAs and biological validation of selected candidates in Agrobacterium tumefaciens. PUBMED:23950988
Thore S, Leibundgut M, Ban N Science. 2006;312:1208-1211. Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand. PUBMED:16675665
Welz R, Breaker RR RNA. 2007;13:573-582. Ligand binding and gene control characteristics of tandem riboswitches in Bacillus anthracis. PUBMED:17307816
Serganov A, Polonskaia A, Phan AT, Breaker RR, Patel DJ Nature. 2006;441:1167-1171. Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch. PUBMED:16728979
Edwards TE, Ferre-D'Amare AR Structure. 2006;14:1459-1468. Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition. PUBMED:16962976
Thore S, Frick C, Ban N J Am Chem Soc. 2008;130:8116-8117. Structural basis of thiamine pyrophosphate analogues binding to the eukaryotic riboswitch. PUBMED:18533652
Kulshina N, Edwards TE, Ferre-D'Amare AR RNA. 2010;16:186-196. Thermodynamic analysis of ligand binding and ligand binding-induced tertiary structure formation by the thiamine pyrophosphate riboswitch. PUBMED:19948769
Warner KD, Homan P, Weeks KM, Smith AG, Abell C, Ferre-D'Amare AR Chem Biol. 2014;21:591-595. Validating fragment-based drug discovery for biological RNAs: lead fragments bind and remodel the TPP riboswitch specifically. PUBMED:24768306

External database links

Gene Ontology:	GO:0030976 (thiamine pyrophosphate binding);
Sequence Ontology:	SO:0000035 (riboswitch);

Curation and family details

This section shows the detailed information about the Rfam family. We're happy to receive updated or improved alignments for new or existing families. Submit your new alignment and we'll take a look.

Curation

Seed source

Vitreshchak A

Structure source

Published; PMID:12376536;

Type

Cis-reg; riboswitch;

Author

Rodionov DA ORCID logo

, Vitreshchak AG, Mironov AA, Gelfand MS ORCID logo

, Bateman A ORCID logo

, Moxon SJ ORCID logo

, Ontiveros-Palacios N ORCID logo

Alignment details

Alignment	Number of sequences
full	16,130
seed	115

Model information

Build commands

cmbuild -F CM SEED

cmcalibrate --mpi CM

Search command

cmsearch --cpu 4 --verbose --nohmmonly -T 30.00 -Z 2958934 CM SEQDB

Gathering cutoff

54.3

Trusted cutoff

54.3

Noise cutoff

54.2

Covariance model

Download

Family: TPP (RF00059)

Description: TPP riboswitch aptamer (THI element)

Summary

Note on Riboswitches

Wikipedia annotation Edit Wikipedia article

Before you edit for the first time

Things you should know

How your contribution will be recorded

Information we would like to see added

Does Rfam agree with the content of the Wikipedia entry ?

Contact us

Sequences

Alignment

Viewing

Downloading

View options

Formatting options

Download

Submit a new alignment

Secondary structure

Acknowledgements

Current Rfam structure

R-scape optimised structure

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Trees

Structures

References

Literature references

External database links

Curation and family details

Curation

Model information

Rfam is part of the ELIXIR infrastructure