Evidence for a group II intron-like catalytic triplex in the spliceosome.

Abstract:

:To catalyze pre-mRNA splicing, U6 small nuclear RNA positions two metals that interact directly with the scissile phosphates. U6 metal ligands correspond stereospecifically to metal ligands within the catalytic domain V of a group II self-splicing intron. Domain V ligands are organized by base-triple interactions, which also juxtapose the 3' splice site with the catalytic metals. However, in the spliceosome, the mechanism for organizing catalytic metals and recruiting the substrate has remained unclear. Here we show by genetics, cross-linking and biochemistry in yeast that analogous triples form in U6 and promote catalytic-metal binding and both chemical steps of splicing. Because the triples include an element that defines the 5' splice site, they also provide a mechanism for juxtaposing the pre-mRNA substrate with the catalytic metals. Our data indicate that U6 adopts a group II intron-like tertiary conformation to catalyze splicing.

journal_name

Nat Struct Mol Biol

authors

Fica SM,Mefford MA,Piccirilli JA,Staley JP

doi

10.1038/nsmb.2815

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

464-471

issue

5

eissn

1545-9993

issn

1545-9985

journal_volume

21

pub_type

杂志文章
  • Chromatin organization marks exon-intron structure.

    abstract::An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from h...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1659

    authors: Schwartz S,Meshorer E,Ast G

    更新日期:2009-09-01 00:00:00

  • Transition states for protein folding have native topologies despite high structural variability.

    abstract::We present a structural analysis of the folding transition states of three SH3 domains. Our results reveal that the secondary structure is not yet fully formed at this stage of folding and that the solvent is only partially excluded from the interior of the protein. Comparison of the members of the transition state en...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb765

    authors: Lindorff-Larsen K,Vendruscolo M,Paci E,Dobson CM

    更新日期:2004-05-01 00:00:00

  • Mechanochemical coupling of two substeps in a single myosin V motor.

    abstract::Myosin V is a double-headed processive molecular motor that moves along an actin filament by taking 36-nm steps. Using optical trapping nanometry with high spatiotemporal resolution, we discovered that there are two possible pathways for the 36-nm steps, one with 12- and 24-nm substeps, in this order, and the other wi...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb806

    authors: Uemura S,Higuchi H,Olivares AO,De La Cruz EM,Ishiwata S

    更新日期:2004-09-01 00:00:00

  • Structural basis for selective activation of ABA receptors.

    abstract::Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discov...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1898

    authors: Peterson FC,Burgie ES,Park SY,Jensen DR,Weiner JJ,Bingman CA,Chang CE,Cutler SR,Phillips GN Jr,Volkman BF

    更新日期:2010-09-01 00:00:00

  • Tertiary interactions within the ribosomal exit tunnel.

    abstract::Although tertiary folding of whole protein domains is prohibited by the cramped dimensions of the ribosomal tunnel, dynamic tertiary interactions may permit folding of small elementary units within the tunnel. To probe this possibility, we used a beta-hairpin and an alpha-helical hairpin from the cytosolic N terminus ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1571

    authors: Kosolapov A,Deutsch C

    更新日期:2009-04-01 00:00:00

  • A popular engagement at the ends.

    abstract::Three recent studies converged on a specific protein-protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells. An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regu...

    journal_title:Nature structural & molecular biology

    pub_type: 新闻

    doi:10.1038/nsmb.2483

    authors: Lue NF,Yu EY,Lei M

    更新日期:2013-01-01 00:00:00

  • Multiple in vivo pathways for Escherichia coli small ribosomal subunit assembly occur on one pre-rRNA.

    abstract::Processing of transcribed precursor ribosomal RNA (pre-rRNA) to a mature state is a conserved aspect of ribosome biogenesis in vivo. We developed an affinity-purification system to isolate and analyze in vivo-formed pre-rRNA-containing ribonucleoprotein (RNP) particles (rRNPs) from wild-type E. coli. We observed that ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2887

    authors: Gupta N,Culver GM

    更新日期:2014-10-01 00:00:00

  • A teacupful of medicine?

    abstract::Green tea has held a long-standing place in traditional Asian medicine. Scientific research is now beginning to explain why. ...

    journal_title:Nature structural & molecular biology

    pub_type: 评论,社论

    doi:10.1038/nsmb0608-537

    authors:

    更新日期:2008-06-01 00:00:00

  • The WAVE regulatory complex is inhibited.

    abstract::The WAVE regulatory complex (WRC) transmits information from the Rac GTPase to the actin nucleator Arp2/3 complex. We have reconstituted recombinant human and Drosophila WRC in several forms and shown that they are inactive toward Arp2/3 complex but can be activated by Rac in a nucleotide-dependent fashion. Our observ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1587

    authors: Ismail AM,Padrick SB,Chen B,Umetani J,Rosen MK

    更新日期:2009-05-01 00:00:00

  • The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock.

    abstract::Cells respond to changes in environmental conditions via orchestrated modifications in gene expression. For example, in response to heat shock, cells execute a program of gene-specific transcriptional activation and repression. Although the activation of genes upon heat shock has been widely studied, the mechanism of ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb813

    authors: Allen TA,Von Kaenel S,Goodrich JA,Kugel JF

    更新日期:2004-09-01 00:00:00

  • MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in telomere length control.

    abstract::Human telomeres are associated with ATM and the protein complex consisting of MRE11, RAD50 and NBS1 (MRN), which are central to maintaining genomic stability. Here we show that when targeted to telomeres, wild-type RAD50 downregulates telomeric association of TRF1, a negative regulator of telomere maintenance. TRF1 bi...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1286

    authors: Wu Y,Xiao S,Zhu XD

    更新日期:2007-09-01 00:00:00

  • 7SK-BAF axis controls pervasive transcription at enhancers.

    abstract::RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a ma...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3176

    authors: Flynn RA,Do BT,Rubin AJ,Calo E,Lee B,Kuchelmeister H,Rale M,Chu C,Kool ET,Wysocka J,Khavari PA,Chang HY

    更新日期:2016-03-01 00:00:00

  • Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2.

    abstract::Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 methylation patterns remain incompletely understood. Epigenetic mechanism...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-018-0036-6

    authors: Højfeldt JW,Laugesen A,Willumsen BM,Damhofer H,Hedehus L,Tvardovskiy A,Mohammad F,Jensen ON,Helin K

    更新日期:2018-03-01 00:00:00

  • Active site remodeling switches HIV specificity of antiretroviral TRIMCyp.

    abstract::TRIMCyps are primate antiretroviral proteins that potently inhibit HIV replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1667

    authors: Price AJ,Marzetta F,Lammers M,Ylinen LM,Schaller T,Wilson SJ,Towers GJ,James LC

    更新日期:2009-10-01 00:00:00

  • Global analysis of yeast mRNPs.

    abstract::Proteins regulate gene expression by controlling mRNA biogenesis, localization, translation and decay. Identifying the composition, diversity and function of mRNA-protein complexes (mRNPs) is essential to understanding these processes. In a global survey of Saccharomyces cerevisiae mRNA-binding proteins, we identified...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2468

    authors: Mitchell SF,Jain S,She M,Parker R

    更新日期:2013-01-01 00:00:00

  • Structure of a purine-purine wobble base pair in the decoding center of the ribosome.

    abstract::Here we report the crystal structures of I.C and I.A wobble base pairs in the context of the ribosomal decoding center, clearly showing that the I.A base pair is of an I(anti).A(anti) conformation, as predicted by Crick. Additionally, the structures enable the observation of changes in the anticodon to allow purine-pu...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb866

    authors: Murphy FV 4th,Ramakrishnan V

    更新日期:2004-12-01 00:00:00

  • An accurately preorganized IRES RNA structure enables eIF4G capture for initiation of viral translation.

    abstract::Many viruses bypass canonical cap-dependent translation in host cells by using internal ribosomal entry sites (IRESs) in their transcripts; IRESs hijack initiation factors for the assembly of initiation complexes. However, it is currently unknown how IRES RNAs recognize initiation factors that have no endogenous RNA b...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3280

    authors: Imai S,Kumar P,Hellen CU,D'Souza VM,Wagner G

    更新日期:2016-09-01 00:00:00

  • Technologies to probe functions and mechanisms of long noncoding RNAs.

    abstract::Thousands of long noncoding RNAs (lncRNAs) have been discovered, but their functional characterization has been slowed by a limited set of research tools. Here we review emerging RNA-centric methods to interrogate the intrinsic structure of lncRNAs as well as their genomic localization and biochemical partners. Unders...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2921

    authors: Chu C,Spitale RC,Chang HY

    更新日期:2015-01-01 00:00:00

  • Separate RNA-binding surfaces on the multifunctional La protein mediate distinguishable activities in tRNA maturation.

    abstract::By sequence-specific binding to 3' UUU-OH, the La protein shields precursor (pre)-RNAs from 3' end digestion and is required to protect defective pre-transfer RNAs from decay. Although La is comprised of a La motif and an RNA-recognition motif (RRM), a recent structure indicates that the RRM beta-sheet surface is not ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1110

    authors: Huang Y,Bayfield MA,Intine RV,Maraia RJ

    更新日期:2006-07-01 00:00:00

  • Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors.

    abstract::Heat-shock transcription factor (HSF) family members function in stress protection and in human diseases including proteopathies, neurodegeneration and cancer. The mechanisms that drive distinct post-translational modifications, cofactor recruitment and target-gene activation for specific HSF paralogs are unknown. We ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3150

    authors: Jaeger AM,Pemble CW 4th,Sistonen L,Thiele DJ

    更新日期:2016-02-01 00:00:00

  • Antisense transcripts are targets for activating small RNAs.

    abstract::Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) h...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1444

    authors: Schwartz JC,Younger ST,Nguyen NB,Hardy DB,Monia BP,Corey DR,Janowski BA

    更新日期:2008-08-01 00:00:00

  • Structural mimicry in transcription regulation of human RNA polymerase II by the DNA helicase RECQL5.

    abstract::RECQL5 is a member of the highly conserved RecQ family of DNA helicases involved in DNA repair. RECQL5 interacts with RNA polymerase II (Pol II) and inhibits transcription of protein-encoding genes by an unknown mechanism. We show that RECQL5 contacts the Rpb1 jaw domain of Pol II at a site that overlaps with the bind...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2596

    authors: Kassube SA,Jinek M,Fang J,Tsutakawa S,Nogales E

    更新日期:2013-07-01 00:00:00

  • Developmental programming of CpG island methylation profiles in the human genome.

    abstract::CpG island-like sequences are commonly thought to provide the sole signals for designating constitutively unmethylated regions in the genome, thus generating open chromatin domains within a sea of global repression. Using a new database obtained from comprehensive microarray analysis, we show that unmethylated regions...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1594

    authors: Straussman R,Nejman D,Roberts D,Steinfeld I,Blum B,Benvenisty N,Simon I,Yakhini Z,Cedar H

    更新日期:2009-05-01 00:00:00

  • Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.

    abstract::SUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1168

    authors: Reverter D,Lima CD

    更新日期:2006-12-01 00:00:00

  • Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA.

    abstract::Bacterial tRNA adenosine deaminases (TadAs) catalyze the hydrolytic deamination of adenosine to inosine at the wobble position of tRNA(Arg2), a process that enables this single tRNA to recognize three different arginine codons in mRNA. In addition, inosine is also introduced at the wobble position of multiple eukaryot...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1047

    authors: Losey HC,Ruthenburg AJ,Verdine GL

    更新日期:2006-02-01 00:00:00

  • Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements.

    abstract::We describe a novel approach to separate two ribosome populations from the same cells and use this method in combination with RNA-seq to identify mRNAs bound to Saccharomyces cerevisiae ribosomes with and without Rps26, a protein linked to the pathogenesis of Diamond-Blackfan anemia (DBA). These analyses reveal that R...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3442

    authors: Ferretti MB,Ghalei H,Ward EA,Potts EL,Karbstein K

    更新日期:2017-09-01 00:00:00

  • An asymmetric interface between the regulatory and core particles of the proteasome.

    abstract::The Saccharomyces cerevisiae proteasome comprises a 19-subunit regulatory particle and a 28-subunit core particle. To be degraded, substrates must cross the core particle-regulatory particle interface, a site for complex conformational changes and regulatory events. This interface includes two aligned heteromeric ring...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2147

    authors: Tian G,Park S,Lee MJ,Huck B,McAllister F,Hill CP,Gygi SP,Finley D

    更新日期:2011-10-30 00:00:00

  • A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators.

    abstract::Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin release and hepatic metabolism, and its loss of function is implicated in diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in diabetes; however, clinical data indicate that their benefits can be offset by hypoglycemia, o...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2717

    authors: Szlyk B,Braun CR,Ljubicic S,Patton E,Bird GH,Osundiji MA,Matschinsky FM,Walensky LD,Danial NN

    更新日期:2014-01-01 00:00:00

  • Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem.

    abstract::Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conser...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb958

    authors: Long JF,Feng W,Wang R,Chan LN,Ip FC,Xia J,Ip NY,Zhang M

    更新日期:2005-08-01 00:00:00

  • Adenine riboswitches and gene activation by disruption of a transcription terminator.

    abstract::A class of riboswitches that recognizes guanine and discriminates against other purine analogs was recently identified. RNAs that carry the consensus sequence and structural features of guanine riboswitches are located in the 5' untranslated region (UTR) of numerous prokaryotic genes, where they control the expression...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb710

    authors: Mandal M,Breaker RR

    更新日期:2004-01-01 00:00:00