词条 | T-box leader |
释义 |
| 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.[1] This interaction controls expression of downstream aminoacyl-tRNA synthetase genes, amino acid biosynthesis, and uptake-related genes in a negative feedback loop.[1][2] The uncharged tRNA acts as the effector for transcription antitermination of genes in the T-box leader family.[3][4][5] 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.[6] tRNA-mediated attenuationAlthough 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.[2] They are structurally complex and able to directly sense physiological signals which results in the control of downstream gene expression.[2] 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).[7] 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.[7] Two of the most crucial segments to attenuation function as both the terminator and the antiterminator in different regulatory situations.[7] Leader structureIn terms of structure, the T box RNA is highly conserved—especially in the stem I distal region.[1] 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.[1] This loop-loop structure is similar to that seen in the ribosome exit site, suggesting that it is highly conserved among tRNA recognition sites.[1] The apex of the stem I region recognizes two critical positions on the tRNA: the anticodon and D/T-loops.[8] Extensive intermolecular interactions occur at this site.[8] 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.[8][9] Riboswitch functionThe riboswitch functions by directly sensing a physiological signal.[10] 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.[2][10] The specifier sequence is the first recognition sequence in the leader.[7] It is complementary to the anticodon of the tRNA that is a substrate of the tRNA synthetase under regulation.[7] The second tRNA binding sequence, the T box sequence, is complementary to the nucleotide preceding the acceptor end of the tRNA.[7] The T box is found in the side bulge of the antiterminator.[7] Method of regulationThe most common model system used to study T-box leader is in the gram-positive bacterium Bacillus subtilis.[10] 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.[7] Without terminator formation, transcription will proceed.[7] If, however, the tRNA is charged, its acceptor end will be blocked by an amino acid and thus, cannot pair with the T box.[7] The terminator will then form, thereby terminating transcription.[7] External links
References1. ^1 2 3 4 {{cite journal|last1=Grigg|first1=JC|last2=Chen|first2=Y|last3=Grundy|first3=FJ|last4=Henkin|first4=TM|last5=Pollack|first5=L|last6=Ke|first6=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=7240–5|pmid=23589841|doi=10.1073/pnas.1222214110|date=Apr 2013|pmc=3645572}} {{portal bar|Biology}}2. ^1 2 3 {{cite journal|last1=Green|first1=NJ|last2=Grundy|first2=FJ|last3=Henkin|first3=TM|title=The T box mechanism: tRNA as a regulatory molecule.|journal=FEBS Letters|volume=584|issue=2|pages=318–24|pmid=19932103|doi=10.1016/j.febslet.2009.11.056|date=Jan 2010|pmc=2794906}} 3. ^{{cite journal|last1=Grundy|first1=FJ|last2=Rollins|first2=SM|last3=Henkin|first3=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=4518–26|pmid=8045882|pmc=196270|date=August 1994}} 4. ^{{cite journal|last1=Grundy|first1=FJ|last2=Collins|first2=JA|last3=Rollins|first3=SM|last4=Henkin|first4=TM|title=tRNA determinants for transcription antitermination of the Bacillus subtilis tyrS gene.|journal=RNA|volume=6|issue=8|pages=1131–41|pmid=10943892|doi=10.1017/s1355838200992100|pmc=1369987|date=August 2000}} 5. ^{{cite journal|last1=Winkler|first1=WC|last2=Grundy|first2=FJ|last3=Murphy|first3=BA|last4=Henkin|first4=TM|title=The GA motif: an RNA element common to bacterial antitermination systems, rRNA, and eukaryotic RNAs.|journal=RNA|volume=7|issue=8|pages=1165–72|pmid=11497434|doi=10.1017/s1355838201002370|pmc=1370163|date=August 2001}} 6. ^{{cite journal|last1=Gerdeman|first1=MS|last2=Henkin|first2=TM|last3=Hines|first3=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|pmid=12547201|doi=10.1016/s0022-2836(02)01339-6|date=February 2003}} 7. ^1 2 3 4 5 6 7 8 9 10 {{cite book|last1=Lederberg|first1=ed.-in-chief: Joshua|title=Encyclopedia of microbiology|publisher=Academic Press|location=San Diego [u.a.]|isbn=0122268008|edition=2.}} 8. ^1 2 {{cite journal|last1=Grigg|first1=JC|last2=Ke|first2=A|title=Structural determinants for geometry and information decoding of tRNA by T box leader RNA.|journal=Structure|volume=21|issue=11|pages=2025–32|pmid=24095061|doi=10.1016/j.str.2013.09.001|date=Nov 2013|pmc=3879790}} 9. ^{{cite journal|last1=Wang|first1=J|last2=Nikonowicz|first2=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|pmid=21333656|doi=10.1016/j.jmb.2011.02.014|date=Apr 2011|pmc=3070822}} 10. ^1 2 {{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|deadurl=yes|archiveurl=https://web.archive.org/web/20141104032041/http://microbiology.osu.edu/faculty/henkin-tina-m|archivedate=2014-11-04|df=}} 2 : Cis-regulatory RNA elements|Gram-positive bacteria |
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