Abstract:
:Regulatory sequences or erroneous incorporations during DNA transcription cause RNA polymerase backtracking and inactivation in all kingdoms of life. Reactivation requires RNA transcript cleavage. Essential transcription factors (GreA and GreB, or TFIIS) accelerate this reaction. We report four cryo-EM reconstructions of Escherichia coli RNA polymerase representing the entire reaction pathway: (1) a backtracked complex; a backtracked complex with GreB (2) before and (3) after RNA cleavage; and (4) a reactivated, substrate-bound complex with GreB before RNA extension. Compared with eukaryotes, the backtracked RNA adopts a different conformation. RNA polymerase conformational changes cause distinct GreB states: a fully engaged GreB before cleavage; a disengaged GreB after cleavage; and a dislodged, loosely bound GreB removed from the active site to allow RNA extension. These reconstructions provide insight into the catalytic mechanism and dynamics of RNA cleavage and extension and suggest how GreB targets backtracked complexes without interfering with canonical transcription.
journal_name
Mol Celljournal_title
Molecular cellauthors
Abdelkareem M,Saint-André C,Takacs M,Papai G,Crucifix C,Guo X,Ortiz J,Weixlbaumer Adoi
10.1016/j.molcel.2019.04.029subject
Has Abstractpub_date
2019-07-25 00:00:00pages
298-309.e4issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(19)30321-1journal_volume
75pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract::Cas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Unbiased detection through proximity labeling ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.06.014
更新日期:2020-07-16 00:00:00
abstract::Dong et al. (2017) establish how the mitochondrial Ca2+ uniporter (MCU) integrates Ca2+ and oxidative stress signals by identifying a cysteine residue that controls MCU channel activity, a mechanism causing mitochondrial Ca2+ overload and cell death during oxidative stress. ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.02.029
更新日期:2017-03-16 00:00:00
abstract::To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2012.05.028
更新日期:2012-06-08 00:00:00
abstract::Trimethylation of histone H3 on lysine 4 (H3K4me3) localizes near the 5' region of genes and is tightly associated with active loci. Several proteins, such as CHD1, BPTF, JMJD2A, and the ING tumor suppressor family, directly recognize this lysine methyl mark. However, how H3K4me3 recognition participates in active tra...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.11.010
更新日期:2007-11-30 00:00:00
abstract::The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.05.028
更新日期:2016-07-07 00:00:00
abstract::Bacterial actin MreB is one of the key components of the bacterial cytoskeleton. It assembles into short filaments that lie just underneath the membrane and organize the cell wall synthesis machinery. Here we show that MreB from both T. maritima and E. coli binds directly to cell membranes. This function is essential ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.07.008
更新日期:2011-08-05 00:00:00
abstract::Nuclear import of proteins containing a classical nuclear localization signal (NLS) involves NLS recognition by importin alpha, which associates with importin beta via the IBB domain. Other proteins, including parathyroid hormone-related protein (PTHrP), are imported into the nucleus by direct interaction with importi...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(02)00727-x
更新日期:2002-12-01 00:00:00
abstract::Molecular motors are the long-haul carriers of eukaryotic cells, moving cargos bidirectionally along microtubule tracks. In the December 12th issue of Cell, report that HDAC6, a tubulin deacetylase, functions as an adaptor that links cargos of aggregated protein to the minus end-directed motor, cytoplasmic dynein. ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(03)00498-2
更新日期:2003-12-01 00:00:00
abstract::During meiosis, recombination between homologous chromosomes generates crossover (CR) and noncrossover (NCR) products. CRs establish connections between homologs, whereas intermediates leading to NCRs have been proposed to participate in homologous pairing. How these events are differentiated and regulated remains to ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2005.09.021
更新日期:2005-11-23 00:00:00
abstract::Stress granules and P-bodies are cytosolic biomolecular condensates that dynamically form by the phase separation of RNAs and proteins. They participate in translational control and buffer the proteome. Upon stress, global translation halts and mRNAs bound to the translational machinery and other proteins coalesce to ...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2019.09.014
更新日期:2019-10-17 00:00:00
abstract::The Mre11-Rad50-Xrs2 (MRX) complex is related to SMC complexes that form rings capable of holding two distinct DNA strands together. MRX functions at stalled replication forks and double-strand breaks (DSBs). A mutation in the N-terminal OB fold of the 70 kDa subunit of yeast replication protein A, rfa1-t11, abrogates...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.10.032
更新日期:2016-12-01 00:00:00
abstract::The carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) comprises multiple heptapeptide repeats of the consensus Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Reversible phosphorylation of Ser2, Ser5, and Ser7 during the transcription cycle mediates the sequential recruitment of transcription/RNA pr...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.11.006
更新日期:2012-01-13 00:00:00
abstract::Cas4 nucleases are conserved factors in many CRISPR systems, yet their molecular role has remained enigmatic. In this issue of Molecular Cell, Shiimori et al. (2018) report that two Cas4 nucleases together determine the size, orientation, and PAM for foreign DNA snippets acquired by CRISPR loci as immunological memory...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2018.05.028
更新日期:2018-06-07 00:00:00
abstract::Whereas most kinesins motor along microtubules, KinI kinesins are microtubule depolymerizing machines. Surprisingly, we found that a KinI fragment consisting of only the motor core is capable of ATP-dependent depolymerization. The motor binds along microtubules in all nucleotide states, but in the presence of AMPPNP, ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(02)00503-8
更新日期:2002-04-01 00:00:00
abstract::Homology-dependent repair of double-strand breaks (DSBs) from nonsister templates has the potential to generate loss of heterozygosity or genome rearrangements. Here we show that the Saccharomyces cerevisiae Mph1 helicase prevents crossovers between ectopic sequences by removing substrates for Mus81-Mms4 or Rad1-Rad10...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2013.09.007
更新日期:2013-10-10 00:00:00
abstract::The anaphase-promoting complex (APC) is a ubiquitin ligase that promotes the degradation of cell-cycle regulators. Cdh1p is an APC coactivator that directly binds APC substrates. A genetic screen in budding yeast identified residues within Cdh1p critical for its function. Cdh1p proteins containing mutations within the...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2005.04.022
更新日期:2005-05-27 00:00:00
abstract::Viral initiators perform multiple functions in initiation of DNA replication including ori binding, melting, and unwinding, culminating in the formation of a double hexameric (DH) helicase. We have recapitulated the assembly of the papillomavirus E1 initiator DH helicase, providing the first description of how such a ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2005.09.020
更新日期:2005-11-11 00:00:00
abstract::Among the five KCNQ channels, also known as the Kv7 voltage-gated potassium (Kv) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological disorders such as epilepsy, deafness, and neuropathic pain. Here, we report the cryoelectron microscopy (cryo-EM) structures...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.10.037
更新日期:2021-01-07 00:00:00
abstract::Proliferating metazoan cells respond to damage that has the potential to cause genomic instability by restricting the cell division cycle or by initiating apoptosis. The molecular mechanisms determining the balance between these responses are not well understood. Here, we show that the apoptotic initiator protease cas...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.03.019
更新日期:2007-04-27 00:00:00
abstract::Group II intron RNPs are mobile genetic elements that attack and invade duplex DNA. In this work, we monitor the invasion reaction in vitro and establish a quantitative kinetic framework for the steps of this complex cascade. We find that target site specificity is achieved after DNA binding, which occurs nonspecifica...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(03)00069-8
更新日期:2003-03-01 00:00:00
abstract::Polymerase gamma, which replicates and repairs mitochondrial DNA, requires the Pol gamma B subunit for processivity. We determined the crystal structure of mouse Pol gamma B, a core component of the mitochondrial replication machinery. Pol gamma B shows high similarity to glycyl-tRNA synthetase and dimerizes through a...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)00153-8
更新日期:2001-01-01 00:00:00
abstract::In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.12.002
更新日期:2017-01-19 00:00:00
abstract::Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oo...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.08.031
更新日期:2018-10-18 00:00:00
abstract::FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)00353-7
更新日期:2001-10-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) activity is regulated by assembly of two functionally distinct complexes, mTORC1 and mTORC2. In syndecan-4 (S4) null endothelial cells, mTORC2 activity is reduced, resulting in decreased Akt activation, while mTORC1 activity is increased. Levels of rictor, mLST8, and mSin-1 are unc...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2008.09.010
更新日期:2008-10-10 00:00:00
abstract::Whipple et al., 2020 describe that, in neurons, a dense cluster of maternally expressed microRNAs post-transcriptionally downregulates several imprinted genes expressed from the paternal genome-an antagonistic mechanism that modulates neuronal functions and provides insights into the evolution of genomic imprinting. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2020.03.019
更新日期:2020-04-02 00:00:00
abstract::Dosage compensation ensures equal expression of X-linked genes in males and females. In Drosophila, equalization is achieved by hypertranscription of the male X chromosome. This process requires an RNA/protein containing dosage compensation complex (DCC). Here we use RNA interference of individual DCC components to de...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(03)00140-0
更新日期:2003-05-01 00:00:00
abstract::DNA double-strand breaks (DSBs) arise during physiological transcription, DNA replication, and antigen receptor diversification. Mistargeting or misprocessing of DSBs can result in pathological structural variation and mutation. Here we describe a sensitive method (END-seq) to monitor DNA end resection and DSBs genome...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.06.034
更新日期:2016-09-01 00:00:00
abstract::Eukaryotic cells license far more origins than are actually used for DNA replication, thereby generating a large number of dormant origins. Accumulating evidence suggests that such origins play a role in chromosome stability and tumor suppression, though the underlying mechanism is largely unknown. Here, we show that ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.02.006
更新日期:2011-03-04 00:00:00
abstract::Apoptosis, a phenomenon that allows the regulated destruction and disposal of damaged or unwanted cells, is common to many cellular processes in multicellular organisms. In humans more than 200 proteins are involved in apoptosis, many of which are dysregulated or defective in human diseases including cancer. A large n...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2005.05.026
更新日期:2005-07-01 00:00:00