Persistence of backtracking by human RNA polymerase II
Yang et al. reveal that human RNA polymerase II often experiences extensive backtracking, leading to persistent entrapment in a backtracked state in vivo. This phenomenon is commonly observed near splice sites and gene starting points and particularly in histones. Persistent backtracking is likely to imp act various gene expression programs significantly. (Source: Molecular Cell)
Source: Molecular Cell - February 9, 2024 Category: Cytology Authors: Kevin B. Yang, Aviram Rasouly, Vitaly Epshtein, Criseyda Martinez, Thao Nguyen, Ilya Shamovsky, Evgeny Nudler Tags: Article Source Type: research
Molecular dynamics-based identification of binding pathways and two distinct high-affinity sites for succinate in succinate receptor 1/GPR91
Extracellular succinate is an auto- and paracrine metabolic stress signal sensed by SUCNR1. Using MD simulations, Shenol et al. found that SUCNR1 has two low-energy binding sites, and its selective activation by high, local concentrations of succinate requires simultaneous occupancy of both high-affinity sites. (Source: Molecular Cell)
Source: Molecular Cell - February 6, 2024 Category: Cytology Authors: Aslihan Shenol, Michael L ückmann, Mette Trauelsen, Matteo Lambrughi, Matteo Tiberti, Elena Papaleo, Thomas M. Frimurer, Thue W. Schwartz Tags: Article Source Type: research
The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs
MiT/TFE transcription factors promote autophagy and lysosomal function. Yang et al. show that the GATOR2 complex inhibits the proteasomal degradation of MiT/TFEs proteins independent of both canonical and non-canonical TORC1 signaling. Thus, the GATOR2 complex independently regulates nutrient-dependent TORC1 activity and the MiT/TFE-dependent maintenance of the lysosomal-auto phagic system. (Source: Molecular Cell)
Source: Molecular Cell - February 6, 2024 Category: Cytology Authors: Shu Yang, Chun-Yuan Ting, Mary A. Lilly Tags: Article Source Type: research
I κBζ is a dual-use coactivator of NF-κB and POU transcription factors
Alpsoy and Wu et al. demonstrate that a well-studied NF-κB regulator, IκBζ, is also a direct binding partner and cofactor of POU transcription factors. These findings implicate IκBζ as an integrator and amplifier of two distinct families of transcription factors at inducible immune genes. (Source: Molecular Cell)
Source: Molecular Cell - February 2, 2024 Category: Cytology Authors: Aktan Alpsoy, Xiaoli S. Wu, Sujay Pal, Olaf Klingbeil, Pramod Kumar, Osama El Demerdash, Benan Nalbant, Christopher R. Vakoc Tags: Short article Source Type: research
Alternative polyadenylation determines the functional landscape of inverted Alu repeats
Ku et al. capture and map the dsRNA structures in the transcriptome to study the pathophysiological role of gene silencing by 3′ UTR IRAlus. Specifically, tumors can suppress p53 via IRAlus exclusion through shortening of MDM2 3′ UTR, whereas global enhancement of IRAlus-mediated gene silencing is a ssociated with neurodegenerative diseases. (Source: Molecular Cell)
Source: Molecular Cell - February 2, 2024 Category: Cytology Authors: Jayoung Ku, Keonyong Lee, Doyeong Ku, Sujin Kim, Jongbin Lee, Hyunwoo Bang, Namwook Kim, Hyunsu Do, Hyeonjung Lee, Chunghun Lim, Jinju Han, Young-suk Lee, Yoosik Kim Tags: Article Source Type: research
Structural basis for plasmid restriction by SMC JET nuclease
The JET nuclease (Wadjet) is a prokaryotic SMC-based defense system that exclusively cleaves plasmid DNA. Roisn é-Hamelin et al. determine structures of plasmid-borne JET, elucidating DNA bending/kinking prior to cleavage. Together with biochemical work, this supports a model of plasmid recognition by SMC motor stalling when circular DNA is completely extruded. (Source: Molecular Cell)
Source: Molecular Cell - February 2, 2024 Category: Cytology Authors: Florian Roisn é-Hamelin, Hon Wing Liu, Michael Taschner, Yan Li, Stephan Gruber Tags: Article Source Type: research
BREACHing new grounds in fragile X syndrome: Trinucleotide expansion linked to genome-wide heterochromatin domains and genome misfolding
In a recent study in Cell, Malachowski et al.1 show that the trinucleotide expansion in the FMR1 gene underlying fragile X syndrome triggers formation of large heterochromatin domains across the genome, resulting in the repression of synaptic genes housed within these domains. (Source: Molecular Cell)
Source: Molecular Cell - February 1, 2024 Category: Cytology Authors: Edda G. Schulz Tags: Spotlight Source Type: research
Out with the old, in with the new: Pioneer transcription factors as activators and repressors of lineage specification genes
In this issue of Molecular Cell, Matsui et al. examine lineage determination by pioneer transcription factors, finding that they control cell fate in cooperation with PRDM family members by repressing alternative-lineage and precocious gene expression through establishment of bivalent enhancers. (Source: Molecular Cell)
Source: Molecular Cell - February 1, 2024 Category: Cytology Authors: Yang Liu, Paul A. Wade Tags: Preview Source Type: research
DNA repair, gap suppression, or fork protection: BRCA2 needs a break!
In this issue of Molecular Cell, Lim et al. reveal new insights into the distinct roles of BRCA2 in coping with DNA breaks, highlighting homologous recombination as the pivotal function that affects tumorigenesis and therapy response. (Source: Molecular Cell)
Source: Molecular Cell - February 1, 2024 Category: Cytology Authors: Diego Dibitetto, Sven Rottenberg Tags: Preview Source Type: research
AlphaFold: Research accelerator and hypothesis generator
To celebrate the 50th anniversary of Cell Press and the Cell special issue focusing on structural biology, we discussed with scientists working across diverse fields how AlphaFold has changed their research and brought structural biology to the masses. (Source: Molecular Cell)
Source: Molecular Cell - February 1, 2024 Category: Cytology Authors: Elizabeth A. Campbell, Helen Walden, Johannes C. Walter, Arun K. Shukla, Martin Beck, Lori A. Passmore, H. Eric Xu Tags: Voices Source Type: research
Meet the authors: Vasty Osei Amponsa and Kylie J. Walters
We talk to Vasty Osei Amponsa and Kylie J. Walters about their paper “hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50”, their journeys across continents leading them to the NCI, and how Kylie tries to foster curiosity and a sense of belonging in her lab. (Source: Molecular Cell)
Source: Molecular Cell - February 1, 2024 Category: Cytology Authors: Vasty Osei Amponsa, Kylie J. Walters Tags: Q & A Source Type: research
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells
Coenzyme Q, a redox lipid crucial for cellular bioenergetics and homeostasis, is synthesized by a multi-step pathway. Here, Pelosi et al. unveil the missing enzyme of the eukaryotic pathway by showing that COQ4 functions as an oxidative decarboxylase on the carbon 1 of coenzyme Q intermediates. (Source: Molecular Cell)
Source: Molecular Cell - January 30, 2024 Category: Cytology Authors: Ludovic Pelosi, Laura Morbiato, Arthur Burgardt, Fiorella Tonello, Abigail K. Bartlett, Rachel M. Guerra, Katayoun Kazemzadeh Ferizhendi, Maria Andrea Desbats, B érengère Rascalou, Marco Marchi, Luis Vázquez-Fonseca, Caterina Agosto, Giuseppe Zanotti, Tags: Short article Source Type: research
Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils
The eukaryotic SMC complexes cohesin, condensin, and the Smc5/6 complex are DNA-loop-extruding motors. Jeppsson et al. show that Smc5/6 preferentially initiates loop extrusion on overtwisted, also called positively supercoiled, DNA. In cells, Smc5/6 is found at sites with transcription-induced positive supercoils, where it controls the spatial organization of chromosomes. (Source: Molecular Cell)
Source: Molecular Cell - January 30, 2024 Category: Cytology Authors: Kristian Jeppsson, Biswajit Pradhan, Takashi Sutani, Toyonori Sakata, Miki Umeda Igarashi, Davide Giorgio Berta, Takaharu Kanno, Ryuichiro Nakato, Katsuhiko Shirahige, Eugene Kim, Camilla Bj örkegren Tags: Article Source Type: research
CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs
Anderson et al. show that expanded CAG trinucleotide repeats produce 3′ splice sites. Proximal donors splice into the repeats in a repeat-length-dependent manner generating unexpected repeat-containing mRNAs. This splicing may place repeats in AUG-initiated frames, potentially explaining aberrant, out-of-fr ame protein products. (Source: Molecular Cell)
Source: Molecular Cell - January 30, 2024 Category: Cytology Authors: Rachel Anderson, Michael R. Das, Yeonji Chang, Kelsey Farenhem, Cameron O. Schmitz, Ankur Jain Tags: Article Source Type: research
Molecular mechanism for target recognition, dimerization, and activation of Pyrococcus furiosus Argonaute
This study provides several insig hts into the working mechanism of long prokaryotic Argonaute. (Source: Molecular Cell)
Source: Molecular Cell - January 30, 2024 Category: Cytology Authors: Longyu Wang, Wanping Chen, Chendi Zhang, Xiaochen Xie, Fuyong Huang, Miaomiao Chen, Wuxiang Mao, Na Yu, Qiang Wei, Lixin Ma, Zhuang Li Tags: Article Source Type: research
