journal
MENU ▼
Read by QxMD icon Read
search

Molecular Cell

journal
https://www.readbyqxmd.com/read/28216226/nbs1-phosphorylation-status-dictates-repair-choice-of-dysfunctional-telomeres
#1
Rekha Rai, Chunyi Hu, Cayla Broton, Yong Chen, Ming Lei, Sandy Chang
Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 Å resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2(TRFH) domain...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431234/tpp1-blocks-an-atr-mediated-resection-mechanism-at-telomeres
#2
Tatsuya Kibe, Michal Zimmermann, Titia de Lange
No abstract text is available yet for this article.
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#3
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431232/genome-wide-mapping-of-drosha-cleavage-sites-on-primary-micrornas-and-noncanonical-substrates
#4
Baekgyu Kim, Kyowon Jeong, V Narry Kim
MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)-specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific positions, DROSHA serves as a main determinant of miRNA sequences and a highly selective gatekeeper for the canonical miRNA pathway. However, the sites of DROSHA-mediated processing have not been annotated, and it remains unclear to what extent DROSHA functions outside the miRNA pathway. Here, we establish a protocol termed "formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq)," which allows identification of DROSHA cleavage sites at single-nucleotide resolution...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431231/sequestration-from-protease-adaptor-confers-differential-stability-to-protease-substrate
#5
Jinki Yeom, Kyle J Wayne, Eduardo A Groisman
According to the N-end rule, the N-terminal residue of a protein determines its stability. In bacteria, the adaptor ClpS mediates proteolysis by delivering substrates bearing specific N-terminal residues to the protease ClpAP. We now report that the Salmonella adaptor ClpS binds to the N terminus of the regulatory protein PhoP, resulting in PhoP degradation by ClpAP. We establish that the PhoP-activated protein MgtC protects PhoP from degradation by outcompeting ClpS for binding to PhoP. MgtC appears to act exclusively on PhoP, as it did not alter the stability of a different ClpS-dependent ClpAP substrate...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431230/structural-basis-for-guide-rna-processing-and-seed-dependent-dna-targeting-by-crispr-cas12a
#6
Daan C Swarts, John van der Oost, Martin Jinek
The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431229/functional-enhancer-screening-in-single-cells
#7
Joris van Arensbergen, Bas van Steensel
In this issue of Molecular Cell, Xie et al. (2017) introduce Mosaic-seq, a powerful technology that combines CRISPRi and single-cell RNA-seq. This method enables the high-throughput assessment of contributions of enhancers to gene regulation.
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431228/a-determined-hesitation-on-h3k27me3-empowers-stem-cells-to-differentiate
#8
Xin Huang, Jianlong Wang
To uncover the precise mechanisms coordinating proliferation and fate choice of stem cells, in this issue of Molecular Cell and in an accompanying paper in Cell Reports, Mazo and colleagues (Petruk et al. 2017a, 2017b) reveal that delayed accumulation of H3K27me3 on nascent DNA is essential to recruit pioneer transcription factors in stem cell differentiation.
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431227/membrane-lipids-speak-to-histones
#9
Yuxiang Zheng, Lewis C Cantley
In this issue of Molecular Cell, Ye et al. (2017) use a combination of genetic, metabolomic, and transcriptomic approaches to explore the potential for methionine metabolism to influence signal transduction and gene expression in budding yeast.
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28416141/multiplexed-engineering-and-analysis-of-combinatorial-enhancer-activity-in-single-cells
#10
Shiqi Xie, Jialei Duan, Boxun Li, Pei Zhou, Gary C Hon
The study of enhancers has been hampered by the scarcity of methods to systematically quantify their endogenous activity. We develop Mosaic-seq to systematically perturb enhancers and measure their endogenous activities at single-cell resolution. Mosaic-seq uses a CRISPR barcoding system to jointly measure a cell's transcriptome and its sgRNA modulators, thus quantifying the effects of dCas9-KRAB-mediated enhancer repression in single cells. Applying Mosaic-seq to 71 constituent enhancers from 15 super-enhancers, our analysis of 51,448 sgRNA-induced transcriptomes finds that only a small number of constituents are major effectors of target gene expression...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28416140/ribonucleotide-reductase-requires-subunit-switching-in-hypoxia-to-maintain-dna-replication
#11
Iosifina P Foskolou, Christian Jorgensen, Katarzyna B Leszczynska, Monica M Olcina, Hanna Tarhonskaya, Bauke Haisma, Vincenzo D'Angiolella, William K Myers, Carmen Domene, Emily Flashman, Ester M Hammond
Cells exposed to hypoxia experience replication stress but do not accumulate DNA damage, suggesting sustained DNA replication. Ribonucleotide reductase (RNR) is the only enzyme capable of de novo synthesis of deoxyribonucleotide triphosphates (dNTPs). However, oxygen is an essential cofactor for mammalian RNR (RRM1/RRM2 and RRM1/RRM2B), leading us to question the source of dNTPs in hypoxia. Here, we show that the RRM1/RRM2B enzyme is capable of retaining activity in hypoxia and therefore is favored over RRM1/RRM2 in order to preserve ongoing replication and avoid the accumulation of DNA damage...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28410996/delayed-accumulation-of-h3k27me3-on-nascent-dna-is-essential-for-recruitment-of-transcription-factors-at-early-stages-of-stem-cell-differentiation
#12
Svetlana Petruk, Jingli Cai, Robyn Sussman, Guizhi Sun, Sina K Kovermann, Samanta A Mariani, Bruno Calabretta, Steven B McMahon, Hugh W Brock, Lorraine Iacovitti, Alexander Mazo
Recruitment of transcription factors (TFs) to repressed genes in euchromatin is essential to activate new transcriptional programs during cell differentiation. However, recruitment of all TFs, including pioneer factors, is impeded by condensed H3K27me3-containing chromatin. Single-cell and gene-specific analyses revealed that, during the first hours of induction of differentiation of mammalian embryonic stem cells (ESCs), accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28392175/structural-basis-of-mycobacterium-tuberculosis-transcription-and-transcription-inhibition
#13
Wei Lin, Soma Mandal, David Degen, Yu Liu, Yon W Ebright, Shengjian Li, Yu Feng, Yu Zhang, Sukhendu Mandal, Yi Jiang, Shuang Liu, Matthew Gigliotti, Meliza Talaue, Nancy Connell, Kalyan Das, Eddy Arnold, Richard H Ebright
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug rifampin (Rif). We report crystal structures of Mtb RNAP, alone and in complex with Rif, at 3.8-4.4 Å resolution. The results identify an Mtb-specific structural module of Mtb RNAP and establish that Rif functions by a steric-occlusion mechanism that prevents extension of RNA. We also report non-Rif-related compounds-Nα-aroyl-N-aryl-phenylalaninamides (AAPs)-that potently and selectively inhibit Mtb RNAP and Mtb growth, and we report crystal structures of Mtb RNAP in complex with AAPs...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28392174/eif5a-functions-globally-in-translation-elongation-and-termination
#14
Anthony P Schuller, Colin Chih-Chien Wu, Thomas E Dever, Allen R Buskirk, Rachel Green
The eukaryotic translation factor eIF5A, originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. Using a combination of ribosome profiling and in vitro biochemistry, we report a much broader role for eIF5A in elongation and uncover a critical function for eIF5A in termination. Ribosome profiling of an eIF5A-depleted strain reveals a global elongation defect, with abundant ribosomes stalling at many sequences, not limited to proline stretches...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28366644/a-metabolic-function-for-phospholipid-and-histone-methylation
#15
Cunqi Ye, Benjamin M Sutter, Yun Wang, Zheng Kuang, Benjamin P Tu
S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here, we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is a major consumer of SAM. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione through transsulfuration...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28388442/cold-signal-shuttles-from-membrane-to-nucleus
#16
Xiaoyu Guo, Shujuan Xu, Kang Chong
In this issue of Molecular Cell, Liu et al. (2017) show that the cold-activated plasma membrane protein kinase CRPK1 phosphorylates 14-3-3 proteins, triggering its nuclear translocation to impair the stabilization of the transcription factor CBFs for a feedback excessive cold defense response during the freezing in Arabidopsis.
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28388441/memory-is-the-treasury-and-guardian-of-all-things
#17
Agustina D'Urso, Jason H Brickner
Transcriptional memory often relies on interactions with nuclear pore proteins. In this issue of Molecular Cell, Pascual-Garcia et al. (2017) describe hormone-induced developmental transcriptional memory in cells that have previously experienced ecdysone, mediated by Nup98-dependent enhancer-promoter looping.
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28388440/genome-and-epigenome-maintenance-by-keeping-histone-turnover-in-check
#18
Anna Fortuny, Sophie E Polo
In this issue of Molecular Cell, Taneja et al. (2017) uncover a dual role for the conserved chromatin remodeler Fft3 in the maintenance of silent heterochromatin and the suppression of replication barriers at euchromatic loci through controlled histone turnover.
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28388439/celastrol-induced-nur77-interaction-with-traf2-alleviates-inflammation-by-promoting-mitochondrial-ubiquitination-and-autophagy
#19
Mengjie Hu, Qiang Luo, Gulimiran Alitongbieke, Shuyi Chong, Chenting Xu, Lei Xie, Xiaohui Chen, Duo Zhang, Yuqi Zhou, Zhaokai Wang, Xiaohong Ye, Lijun Cai, Fang Zhang, Huibin Chen, Fuquan Jiang, Hui Fang, Shanjun Yang, Jie Liu, Maria T Diaz-Meco, Ying Su, Hu Zhou, Jorge Moscat, Xiangzhi Lin, Xiao-Kun Zhang
Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28388438/lsm12-and-me31b-ddx6-define-distinct-modes-of-posttranscriptional-regulation-by-ataxin-2-protein-complex-in-drosophila-circadian-pacemaker-neurons
#20
Jongbo Lee, Eunseok Yoo, Hoyeon Lee, Keunhee Park, Jin-Hoe Hur, Chunghun Lim
ATAXIN-2 (ATX2) has been implicated in human neurodegenerative diseases, yet it remains elusive how ATX2 assembles specific protein complexes to execute its physiological roles. Here we employ the posttranscriptional co-activator function of Drosophila ATX2 to demonstrate that LSM12 and ME31B/DDX6 are two ATX2-associating factors crucial for sustaining circadian rhythms. LSM12 acts as a molecular adaptor for the recruitment of TWENTY-FOUR (TYF) to ATX2. The ATX2-LSM12-TYF complex thereby stimulates TYF-dependent translation of the rate-limiting clock gene period (per) to maintain 24 hr periodicity in circadian behaviors...
April 6, 2017: Molecular Cell
journal
journal
32927
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"