T-box leader
{{Short description|RNA element}}
{{For|the eukaryotic transcription factor family|T-box}}
{{Infobox rfam
| Name = T-box leader
| image = RF00230.jpg
| width =
| caption = Predicted secondary structure and sequence conservation of T-box
| Symbol = T-box
| AltSymbols =
| Rfam = RF00230
| miRBase =
| miRBase_family =
| RNA_type = Cis-reg; leader;
| Tax_domain = Bacteria
| GO = {{GO|0000049}}
| SO = {{SO|0000140}}
| CAS_number =
| EntrezGene =
| HGNCid =
| OMIM =
| PDB =
| RefSeq =
| Chromosome =
| Arm =
| Band =
| LocusSupplementaryData =
}}
Usually found in gram-positive bacteria, the T box leader sequence is an RNA element that controls gene expression through the regulation of translation by binding directly to a specific tRNA and sensing its aminoacylation state.{{cite journal | vauthors = Grigg JC, Chen Y, Grundy FJ, Henkin TM, Pollack L, Ke A | title = T box RNA decodes both the information content and geometry of tRNA to affect gene expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 18 | pages = 7240–7245 | date = April 2013 | pmid = 23589841 | pmc = 3645572 | doi = 10.1073/pnas.1222214110 | bibcode = 2013PNAS..110.7240G | doi-access = free }} This interaction controls expression of downstream aminoacyl-tRNA synthetase genes, amino acid biosynthesis, and uptake-related genes in a negative feedback loop.{{cite journal | vauthors = Green NJ, Grundy FJ, Henkin TM | title = The T box mechanism: tRNA as a regulatory molecule | journal = FEBS Letters | volume = 584 | issue = 2 | pages = 318–324 | date = January 2010 | pmid = 19932103 | pmc = 2794906 | doi = 10.1016/j.febslet.2009.11.056 }} The uncharged tRNA acts as the effector for transcription antitermination of genes in the T-box leader family.{{cite journal | vauthors = Grundy FJ, Rollins SM, Henkin TM | title = Interaction between the acceptor end of tRNA and the T box stimulates antitermination in the Bacillus subtilis tyrS gene: a new role for the discriminator base | journal = Journal of Bacteriology | volume = 176 | issue = 15 | pages = 4518–4526 | date = August 1994 | pmid = 8045882 | pmc = 196270 | doi = 10.1128/jb.176.15.4518-4526.1994 }}{{cite journal | vauthors = Grundy FJ, Collins JA, Rollins SM, Henkin TM | title = tRNA determinants for transcription antitermination of the Bacillus subtilis tyrS gene | journal = RNA | volume = 6 | issue = 8 | pages = 1131–1141 | date = August 2000 | pmid = 10943892 | pmc = 1369987 | doi = 10.1017/s1355838200992100 }}{{cite journal | vauthors = Winkler WC, Grundy FJ, Murphy BA, Henkin TM | title = The GA motif: an RNA element common to bacterial antitermination systems, rRNA, and eukaryotic RNAs | journal = RNA | volume = 7 | issue = 8 | pages = 1165–1172 | date = August 2001 | pmid = 11497434 | pmc = 1370163 | doi = 10.1017/s1355838201002370 }} The anticodon of a specific tRNA base pairs to a specifier sequence within the T-box motif, and the NCCA acceptor tail of the tRNA base pairs to a conserved bulge in the T-box antiterminator hairpin.{{cite journal | vauthors = Gerdeman MS, Henkin TM, Hines JV | title = Solution structure of the Bacillus subtilis T-box antiterminator RNA: seven nucleotide bulge characterized by stacking and flexibility | journal = Journal of Molecular Biology | volume = 326 | issue = 1 | pages = 189–201 | date = February 2003 | pmid = 12547201 | doi = 10.1016/s0022-2836(02)01339-6 }}
tRNA-mediated attenuation
Although the exact mechanism of T box leader is still unclear and currently being studied, it has recently been recognized as a member of an expanding group of RNAs that are phylogenetically conserved across many gram-positive bacteria. They are structurally complex and able to directly sense physiological signals which results in the control of downstream gene expression. This controlling of gene expression is accomplished by transcriptional attenuation—a general transcriptional regulation strategy that senses when an alteration in the rate of transcription is necessary and initiating alteration at a particular site (sometimes preceding one or more genes of an operon).{{cite book|last1=Lederberg|first1=ed.-in-chief: Joshua|title=Encyclopedia of microbiology|year=2000|publisher=Academic Press|location=San Diego [u.a.]|isbn=978-0-12-226800-7|edition=2.|url-access=registration|url=https://archive.org/details/encyclopediaofmi02edunse}} The operons that encode aminoacyl-tRNA synthetases, regulated by tRNA-mediated transcriptional attenuation, contain a leader region that specifies a transcript segment that can fold and eventually form a complex set of structures. Two of the most crucial segments to attenuation function as both the terminator and the antiterminator in different regulatory situations.
Leader structure
In terms of structure, the T box RNA is highly conserved—especially in the stem I distal region. The stem I region forms an arched conformation, with the apex containing a complex loop-loop interaction between the conserved adenine-guanine bulge and distal loop. This loop-loop structure is similar to that seen in the ribosome exit site, suggesting that it is highly conserved among tRNA recognition sites. The apex of the stem I region recognizes two critical positions on the tRNA: the anticodon and D/T-loops.{{cite journal | vauthors = Grigg JC, Ke A | title = Structural determinants for geometry and information decoding of tRNA by T box leader RNA | journal = Structure | volume = 21 | issue = 11 | pages = 2025–2032 | date = November 2013 | pmid = 24095061 | pmc = 3879790 | doi = 10.1016/j.str.2013.09.001 }} Extensive intermolecular interactions occur at this site. If the length or orientation of these two recognition points is altered or mismatched, the T box riboswitch and tRNA complex is disrupted, and proper functioning of transcriptional regulation cannot occur.{{cite journal | vauthors = Wang J, Nikonowicz EP | title = Solution structure of the K-turn and Specifier Loop domains from the Bacillus subtilis tyrS T-box leader RNA | journal = Journal of Molecular Biology | volume = 408 | issue = 1 | pages = 99–117 | date = April 2011 | pmid = 21333656 | pmc = 3070822 | doi = 10.1016/j.jmb.2011.02.014 }}
Riboswitch function
The riboswitch functions by directly sensing a physiological signal.{{cite web|last1=Henkin|first1=Tina|title=Research Interests|url=http://microbiology.osu.edu/faculty/henkin-tina-m|website=The Ohio State University: Department of Microbiology|url-status=dead|archive-url=https://web.archive.org/web/20141104032041/http://microbiology.osu.edu/faculty/henkin-tina-m|archive-date=2014-11-04}} Next, a specific uncharged tRNA binds to a riboswitch element in the transcript, and a structural change occurs in the transcript that promotes expression of the downstream coding sequence. The specifier sequence is the first recognition sequence in the leader. It is complementary to the anticodon of the tRNA that is a substrate of the tRNA synthetase under regulation. The second tRNA binding sequence, the T box sequence, is complementary to the nucleotide preceding the acceptor end of the tRNA. The T box is found in the side bulge of the antiterminator.
Method of regulation
The most common model system used to study T-box leader is in the gram-positive bacterium Bacillus subtilis. In terms of what is currently understood about the regulatory role of T box function, it appears that when the uncharged tRNA is abundant, it binds to the specifier and the T box sequence of an appropriate leader RNA, stabilizing the antiterminator and, in turn, preventing terminator formation. Without terminator formation, transcription will proceed. If, however, the tRNA is charged, its acceptor end will be blocked by an amino acid and thus, cannot pair with the T box. The terminator will then form, thereby terminating transcription.
External links
- {{Rfam|id=RF00230|name=T-box leader}}
- [https://tbdb.io TBDB], a database of annotated T-box leader sequences
References
{{Reflist}}
Category:Cis-regulatory RNA elements
Category:Gram-positive bacteria
{{portal bar|Biology}}