journal
MENU ▼
Read by QxMD icon Read
search

Molecular Cell

journal
https://www.readbyqxmd.com/read/28712727/error-prone-splicing-controlled-by-the-ubiquitin-relative-hub1
#1
Ramazan Karaduman, Sittinan Chanarat, Boris Pfander, Stefan Jentsch
Accurate pre-mRNA splicing is needed for correct gene expression and relies on faithful splice site recognition. Here, we show that the ubiquitin-like protein Hub1 binds to the DEAD-box helicase Prp5, a key regulator of early spliceosome assembly, and stimulates its ATPase activity thereby enhancing splicing and relaxing fidelity. High Hub1 levels enhance splicing efficiency but also cause missplicing by tolerating suboptimal splice sites and branchpoint sequences. Notably, Prp5 itself is regulated by a Hub1-dependent negative feedback loop...
July 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28712726/sengers-syndrome-associated-mitochondrial-acylglycerol-kinase-is-a-subunit-of-the-human-tim22-protein-import-complex
#2
Yilin Kang, David A Stroud, Michael J Baker, David P De Souza, Ann E Frazier, Michael Liem, Dedreia Tull, Suresh Mathivanan, Malcolm J McConville, David R Thorburn, Michael T Ryan, Diana Stojanovski
Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that catalyzes the phosphorylation of monoacylglycerol and diacylglycerol to lysophosphatidic acid and phosphatidic acid, respectively. Mutations in AGK cause Sengers syndrome, which is characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Here we identified AGK as a subunit of the mitochondrial TIM22 protein import complex. We show that AGK functions in a kinase-independent manner to maintain the integrity of the TIM22 complex, where it facilitates the import and assembly of mitochondrial carrier proteins...
July 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28712728/hexim1-and-neat1-long-non-coding-rna-form-a-multi-subunit-complex-that-regulates-dna-mediated-innate-immune-response
#3
Mehdi Morchikh, Alexandra Cribier, Raoul Raffel, Sonia Amraoui, Julien Cau, Dany Severac, Emeric Dubois, Olivier Schwartz, Yamina Bennasser, Monsef Benkirane
The DNA-mediated innate immune response underpins anti-microbial defenses and certain autoimmune diseases. Here we used immunoprecipitation, mass spectrometry, and RNA sequencing to identify a ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1 that we dubbed the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP). The HDP-RNP contains DNA-PK subunits (DNAPKc, Ku70, and Ku80) and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATRIN3). We show that binding of HEXIM1 to NEAT1 is required for its assembly...
July 10, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28712724/acylglycerol-kinase-mutated-in-sengers-syndrome-is-a-subunit-of-the-tim22-protein-translocase-in-mitochondria
#4
Milena Vukotic, Hendrik Nolte, Tim König, Shotaro Saita, Maria Ananjew, Marcus Krüger, Takashi Tatsuta, Thomas Langer
Mutations in mitochondrial acylglycerol kinase (AGK) cause Sengers syndrome, which is characterized by cataracts, hypertrophic cardiomyopathy, and skeletal myopathy. AGK generates phosphatidic acid and lysophosphatidic acid, bioactive phospholipids involved in lipid signaling and the regulation of tumor progression. However, the molecular mechanisms of the mitochondrial pathology remain enigmatic. Determining its mitochondrial interactome, we have identified AGK as a constituent of the TIM22 complex in the mitochondrial inner membrane...
July 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28689659/bcl3-phosphorylation-by-akt-erk2-and-ikk-is-required-for-its-transcriptional-activity
#5
Vivien Ya-Fan Wang, Yidan Li, Daniel Kim, Xiangyang Zhong, Qian Du, Majid Ghassemian, Gourisankar Ghosh
Unlike prototypical IκB proteins, which are inhibitors of NF-κB RelA, cRel, and RelB dimers, the atypical IκB protein Bcl3 is primarily a transcriptional coregulator of p52 and p50 homodimers. Bcl3 exists as phospho-protein in many cancer cells. Unphosphorylated Bcl3 acts as a classical IκB-like inhibitor and removes p50 and p52 from bound DNA. Neither the phosphorylation site(s) nor the kinase(s) phosphorylating Bcl3 is known. Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3...
July 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28689662/activation-of-the-unfolded-protein-response-by-lipid-bilayer-stress
#6
Kristina Halbleib, Kristina Pesek, Roberto Covino, Harald F Hofbauer, Dorith Wunnicke, Inga Hänelt, Gerhard Hummer, Robert Ernst
The unfolded protein response (UPR) is a conserved homeostatic program that is activated by misfolded proteins in the lumen of the endoplasmic reticulum (ER). Recently, it became evident that aberrant lipid compositions of the ER membrane, referred to as lipid bilayer stress, are equally potent in activating the UPR. The underlying molecular mechanism, however, remained unclear. We show that the most conserved transducer of ER stress, Ire1, uses an amphipathic helix (AH) to sense membrane aberrancies and control UPR activity...
June 29, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28673540/single-cell-alternative-splicing-analysis-with-expedition-reveals-splicing-dynamics-during-neuron-differentiation
#7
Yan Song, Olga B Botvinnik, Michael T Lovci, Boyko Kakaradov, Patrick Liu, Jia L Xu, Gene W Yeo
Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational framework consisting of outrigger, a de novo splice graph transversal algorithm to detect AS; anchor, a Bayesian approach to assign modalities; and bonvoyage, a visualization tool using non-negative matrix factorization to display modality changes...
June 28, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28673543/autogenous-control-of-5-top-mrna-stability-by-40s-ribosomes
#8
Antonio Gentilella, Francisco D Morón-Duran, Pedro Fuentes, Guilherme Zweig-Rocha, Ferran Riaño-Canalias, Joffrey Pelletier, Marta Ruiz, Gemma Turón, Julio Castaño, Albert Tauler, Clara Bueno, Pablo Menéndez, Sara C Kozma, George Thomas
Ribosomal protein (RP) expression in higher eukaryotes is regulated translationally through the 5'TOP sequence. This mechanism evolved to more rapidly produce RPs on demand in different tissues. Here we show that 40S ribosomes, in a complex with the mRNA binding protein LARP1, selectively stabilize 5'TOP mRNAs, with disruption of this complex leading to induction of the impaired ribosome biogenesis checkpoint (IRBC) and p53 stabilization. The importance of this mechanism is underscored in 5q(-) syndrome, a macrocytic anemia caused by a large monoallelic deletion, which we found to also encompass the LARP1 gene...
June 26, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28673542/bet-bromodomain-proteins-function-as-master-transcription-elongation-factors-independent-of-cdk9-recruitment
#9
Georg E Winter, Andreas Mayer, Dennis L Buckley, Michael A Erb, Justine E Roderick, Sarah Vittori, Jaime M Reyes, Julia di Iulio, Amanda Souza, Christopher J Ott, Justin M Roberts, Rhamy Zeid, Thomas G Scott, Joshiawa Paulk, Kate Lachance, Calla M Olson, Shiva Dastjerdi, Sophie Bauer, Charles Y Lin, Nathanael S Gray, Michelle A Kelliher, L Stirling Churchman, James E Bradner
Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting event in human gene control. A small number of regulatory factors influence transcription elongation on a global scale. Prior research using small-molecule BET bromodomain inhibitors, such as JQ1, linked BRD4 to context-specific elongation at a limited number of genes associated with massive enhancer regions. Here, the mechanistic characterization of an optimized chemical degrader of BET bromodomain proteins, dBET6, led to the unexpected identification of BET proteins as master regulators of global transcription elongation...
June 23, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28689656/body-temperature-cycles-control-rhythmic-alternative-splicing-in-mammals
#10
Marco Preußner, Gesine Goldammer, Alexander Neumann, Tom Haltenhof, Pia Rautenstrauch, Michaela Müller-McNicoll, Florian Heyd
The core body temperature of all mammals oscillates with the time of the day. However, direct molecular consequences of small, physiological changes in body temperature remain largely elusive. Here we show that body temperature cycles drive rhythmic SR protein phosphorylation to control an alternative splicing (AS) program. A temperature change of 1°C is sufficient to induce a concerted splicing switch in a large group of functionally related genes, rendering this splicing-based thermometer much more sensitive than previously described temperature-sensing mechanisms...
June 22, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28673541/a-novel-rna-phosphorylation-state-enables-5-end-dependent-degradation-in-escherichia-coli
#11
Daniel J Luciano, Nikita Vasilyev, Jamie Richards, Alexander Serganov, Joel G Belasco
RNA modifications that once escaped detection are now thought to be pivotal for governing RNA lifetimes in both prokaryotes and eukaryotes. For example, converting the 5'-terminal triphosphate of bacterial transcripts to a monophosphate triggers 5' end-dependent degradation by RNase E. However, the existence of diphosphorylated RNA in bacteria has never been reported, and no biological role for such a modification has ever been proposed. By using a novel assay, we show here for representative Escherichia coli mRNAs that ∼35%-50% of each transcript is diphosphorylated...
June 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28673544/ttc19-plays-a-husbandry-role-on-uqcrfs1-turnover-in-the-biogenesis-of-mitochondrial-respiratory-complex-iii
#12
Emanuela Bottani, Raffaele Cerutti, Michael E Harbour, Sabrina Ravaglia, Sukru Anil Dogan, Carla Giordano, Ian M Fearnley, Giulia D'Amati, Carlo Viscomi, Erika Fernandez-Vizarra, Massimo Zeviani
Loss-of-function mutations in TTC19 (tetra-tricopeptide repeat domain 19) have been associated with severe neurological phenotypes and mitochondrial respiratory chain complex III deficiency. We previously demonstrated the mitochondrial localization of TTC19 and its link with complex III biogenesis. Here we provide detailed insight into the mechanistic role of TTC19, by investigating a Ttc19(-/-) mouse model that shows progressive neurological and metabolic decline, decreased complex III activity, and increased production of reactive oxygen species...
June 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28732207/a-crispr-resource-for-individual-combinatorial-or-multiplexed-gene-knockout
#13
Nicolas Erard, Simon R V Knott, Gregory J Hannon
We have combined a machine-learning approach with other strategies to optimize knockout efficiency with the CRISPR/Cas9 system. In addition, we have developed a multiplexed sgRNA expression strategy that promotes the functional ablation of single genes and allows for combinatorial targeting. These strategies have been combined to design and construct a genome-wide, sequence-verified, arrayed CRISPR library. This resource allows single-target or combinatorial genetic screens to be carried out at scale in a multiplexed or arrayed format...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28732206/a-utx-mll4-p300-transcriptional-regulatory-network-coordinately-shapes-active-enhancer-landscapes-for-eliciting-transcription
#14
Shu-Ping Wang, Zhanyun Tang, Chun-Wei Chen, Miho Shimada, Richard P Koche, Lan-Hsin Wang, Tomoyoshi Nakadai, Alan Chramiec, Andrei V Krivtsov, Scott A Armstrong, Robert G Roeder
Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1(+)/H3K27ac(+)) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28732205/unique-roles-of-the-non-identical-mcm-subunits-in-dna-replication-licensing
#15
REVIEW
Yuanliang Zhai, Ningning Li, Hanlun Jiang, Xuhui Huang, Ning Gao, Bik Kwoon Tye
A family of six homologous subunits, Mcm2, -3, -4, -5, -6, and -7, each with its own unique features, forms the catalytic core of the eukaryotic replicative helicase. The necessity of six similar but non-identical subunits has been a mystery since its initial discovery. Recent cryo-EM structures of the Mcm2-7 (MCM) double hexamer, its precursors, and the origin recognition complex (ORC)-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate showed that each of these subunits plays a distinct role in orchestrating the assembly of the pre-replication complex (pre-RC) by ORC-Cdc6 and Cdt1...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28732204/put-your-mark-where-your-damage-is-acetyl-coa-production-by-acly-promotes-dna-repair
#16
Samantha J Linder, Raul Mostoslavsky
In this issue of Molecular Cell, Sivanand et al. (2017) describe the importance for nuclear ACLY-mediated production of acetyl-CoA, which promotes histone acetylation, BRCA1 recruitment, and subsequent HR-mediated DNA repair in response to DNA damage, thus drawing a direct link between DNA repair and cellular metabolism.
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28732203/antiviral-immunity-and-circular-rna-no-end-in-sight
#17
Cristhian Cadena, Sun Hur
In this issue of Molecular Cell, two papers by Chen et al. (2017) and Li et al. (2017) describe new insights into circRNA biogenesis and function, connecting circRNAs to innate immune pathways.
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28712725/dynamic-organization-of-chromatin-domains-revealed-by-super-resolution-live-cell-imaging
#18
Tadasu Nozaki, Ryosuke Imai, Mai Tanbo, Ryosuke Nagashima, Sachiko Tamura, Tomomi Tani, Yasumasa Joti, Masaru Tomita, Kayo Hibino, Masato T Kanemaki, Kerstin S Wendt, Yasushi Okada, Takeharu Nagai, Kazuhiro Maeshima
The eukaryotic genome is organized within cells as chromatin. For proper information output, higher-order chromatin structures can be regulated dynamically. How such structures form and behave in various cellular processes remains unclear. Here, by combining super-resolution imaging (photoactivated localization microscopy [PALM]) and single-nucleosome tracking, we developed a nuclear imaging system to visualize the higher-order structures along with their dynamics in live mammalian cells. We demonstrated that nucleosomes form compact domains with a peak diameter of ∼160 nm and move coherently in live cells...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28712723/msp1-is-a-membrane-protein-dislocase-for-tail-anchored-proteins
#19
Matthew L Wohlever, Agnieszka Mateja, Philip T McGilvray, Kasey J Day, Robert J Keenan
Mislocalized tail-anchored (TA) proteins of the outer mitochondrial membrane are cleared by a newly identified quality control pathway involving the conserved eukaryotic protein Msp1 (ATAD1 in humans). Msp1 is a transmembrane AAA-ATPase, but its role in TA protein clearance is not known. Here, using purified components reconstituted into proteoliposomes, we show that Msp1 is both necessary and sufficient to drive the ATP-dependent extraction of TA proteins from the membrane. A crystal structure of the Msp1 cytosolic region modeled into a ring hexamer suggests that active Msp1 contains a conserved membrane-facing surface adjacent to a central pore...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28689661/nuclear-acetyl-coa-production-by-acly-promotes-homologous-recombination
#20
Sharanya Sivanand, Seth Rhoades, Qinqin Jiang, Joyce V Lee, Joseph Benci, Jingwen Zhang, Salina Yuan, Isabella Viney, Steven Zhao, Alessandro Carrer, Michael J Bennett, Andy J Minn, Aalim M Weljie, Roger A Greenberg, Kathryn E Wellen
While maintaining the integrity of the genome and sustaining bioenergetics are both fundamental functions of the cell, potential crosstalk between metabolic and DNA repair pathways is poorly understood. Since histone acetylation plays important roles in DNA repair and is sensitive to the availability of acetyl coenzyme A (acetyl-CoA), we investigated a role for metabolic regulation of histone acetylation during the DNA damage response. In this study, we report that nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia telangiectasia mutated (ATM) and AKT following DNA damage...
July 20, 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"