Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis
Shi et  al. identify a dual regulation of the putative mitochondrial glutathione transporter SLC25A39 by mitochondrial protease AFG3L2 and iron sensing, which enables an autoregulatory mechanism orchestrating glutathione and iron metabolism in mitochondria. (Source: Molecular Cell)
Source: Molecular Cell - December 28, 2023 Category: Cytology Authors: Xiaojian Shi, Marisa DeCiucis, Kariona A. Grabinska, Jean Kanyo, Adam Liu, Tukiet T. Lam, Hongying Shen Tags: Short article Source Type: research

hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF- κB p50
Osei-Amponsa et  al. discover hRpn13 interaction with epigenetic factors physically and functionally both on and off proteasomes and contribution to NF-κB p50 production. These and additionally identified hRpn13 transcriptional requirements provide insights into its cellular impact beyond its known role at protea somes and rationale for anti-cancer activities of hRpn13 PROTACs. (Source: Molecular Cell)
Source: Molecular Cell - December 26, 2023 Category: Cytology Authors: Vasty Osei-Amponsa, Monika Chandravanshi, Xiuxiu Lu, Valentin Magidson, Sudipto Das, Thorkell Andresson, Marzena Dyba, Venkata R. Sabbasani, Rolf E. Swenson, Caroline Fromont, Biraj Shrestha, Yongmei Zhao, Michelle E. Clapp, Raj Chari, Kylie J. Walters Tags: Article Source Type: research

A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass
Sun et  al. identify PPTC7 as a mitophagy sensor that controls the degradation of mitophagy receptors BNIP3 and NIX by scaffolding the assembly of a BNIP3/NIX-PPTC7-SCFFBXL4 holocomplex. PPTC7 represses basal mitophagy to prevent mitochondrial loss and perinatal lethality in mice. It is also upregulated b y fasting to maintain liver mitochondrial mass and metabolic homeostasis. (Source: Molecular Cell)
Source: Molecular Cell - December 26, 2023 Category: Cytology Authors: Yuqiu Sun, Yu Cao, Huayun Wan, Adalet Memetimin, Yang Cao, Lin Li, Chongyang Wu, Meng Wang, She Chen, Qi Li, Yan Ma, Mengqiu Dong, Hui Jiang Tags: Article Source Type: research

Collisions of RNA polymerases behind the replication fork promote alternative RNA splicing in newly replicated chromatin
Bruno et  al. reveal that chromatin replication and transcription-replication conflicts transiently alter transcriptional activity and RNA synthesis both quantitatively and qualitatively. These findings unveil how cell division serves as a source of gene expression variability that can contribute to regulat ing changes in cell identity. (Source: Molecular Cell)
Source: Molecular Cell - December 26, 2023 Category: Cytology Authors: Federica Bruno, Crist óbal Coronel-Guisado, Cristina González-Aguilera Tags: Article Source Type: research

The UFM1 system: Working principles, cellular functions, and pathophysiology
A growing body of evidence is accumulating to show the importance of the UFM1 system in the endoplasmic reticulum (ER), such as ER-phagy and ER-RQC. In this review, we will introduce the mechanisms and cellular functions of the UFM1 system in the ER as well as its pathophysiological roles. (Source: Molecular Cell)
Source: Molecular Cell - December 22, 2023 Category: Cytology Authors: Masaaki Komatsu, Toshifumi Inada, Nobuo N. Noda Tags: Review Source Type: research

High-throughput PRIME-editing screens identify functional DNA variants in the human genome
Ren et  al. present PRIME, a genome-scale method to characterize genome sequences by prime editing at the single-base resolution. PRIME enables the analysis of functional DNA elements at the nucleotide resolution by introducing all possible nucleotide substitutions. Additionally, PRIME can be leveraged to characterize disease-associated genetic variations at scale. (Source: Molecular Cell)
Source: Molecular Cell - December 21, 2023 Category: Cytology Authors: Xingjie Ren, Han Yang, Jovia L. Nierenberg, Yifan Sun, Jiawen Chen, Cooper Beaman, Thu Pham, Mai Nobuhara, Maya Asami Takagi, Vivek Narayan, Yun Li, Elad Ziv, Yin Shen Tags: Technology Source Type: research

Subcytoplasmic location of translation controls protein output
Horste et  al. find that mRNA transcripts that encode non-membrane proteins are not evenly distributed across the cytoplasm. Instead, functionally related groups of transcripts are enriched in compartments that are not separated by membranes. The localization pattern correlates with gene architecture feature s and the binding pattern of 3′ UTR-bound RNA-binding proteins. (Source: Molecular Cell)
Source: Molecular Cell - December 21, 2023 Category: Cytology Authors: Ellen L. Horste, Mervin M. Fansler, Ting Cai, Xiuzhen Chen, Sibylle Mitschka, Gang Zhen, Flora C.Y. Lee, Jernej Ule, Christine Mayr Tags: Article Source Type: research

The case of the missing Ks: Base editor screen to assess cellular fitness at single lysines
In this issue of Molecular Cell, Bao et  al. set out to elucidate “functional lysines” in the genome using adenine base editors. The study reveals several cases of alteration of functions that previous canonical CRISPR-Cas9 screens were unable to detect. (Source: Molecular Cell)
Source: Molecular Cell - December 21, 2023 Category: Cytology Authors: Varun Gopala Krishna, Verena Gudrun Gautsch, Vincenzo D ’Angiolella Tags: Preview Source Type: research

Meet the authors: Yu Zhou, Ting Shan, and Feiyan Liu
We talk to authors Yu Zhou, Ting Shan, and Feiyan Liu about their paper “m6A modification negatively regulates translation by switching mRNA from polysome to P-body via IGF2BP3” (in this issue of Molecular Cell), their passion for RNA biology, and what it’s like leading a “wet and dry” lab. (Source: Molecular Cell)
Source: Molecular Cell - December 21, 2023 Category: Cytology Authors: Yu Zhou, Ting Shan, Feiyan Liu Tags: Q & A Source Type: research

SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis
Zhao et  al. use RIC-seq technology for global profiling of SARS-CoV-2-to-host RNA-RNA interactions in infected cells. The authors find that SARS-CoV-2 RNA stabilizes host mRNAs through their 3′ UTRs via base pairings by recruiting RNA-binding protein YBX3. The stabilized host mRNA NFKBIZ may contribute to SARS-CoV-2-elicited immunopathogenesis. (Source: Molecular Cell)
Source: Molecular Cell - December 20, 2023 Category: Cytology Authors: Hailian Zhao, Zhaokui Cai, Jian Rao, Di Wu, Lei Ji, Rong Ye, Di Wang, Juan Chen, Changchang Cao, Naijing Hu, Ting Shu, Ping Zhu, Jianwei Wang, Xi Zhou, Yuanchao Xue Tags: Article Source Type: research

Mechanisms underlying sensing of cellular stress signals by mammalian MAP3 kinases
Stress-associated MAP kinase signaling requires the sensing of physical and chemical stress signals by upstream MAP3 kinases. Mordente, Ryder, and Bekker-Jensen review the current knowledge of mechanisms by which the large and diverse group of MAP3 kinases with 24 human family members sense cellular stress signals. (Source: Molecular Cell)
Source: Molecular Cell - December 19, 2023 Category: Cytology Authors: Kelly Mordente, Laura Ryder, Simon Bekker-Jensen Tags: Review Source Type: research

The competitive landscape of the dsRNA world
Recognition of foreign and endogenous dsRNAs is complicated by the sequence-independent binding of dsRNA-binding proteins. Cottrell, Andrews, and Bass review the synthesis, processing, binding, and degradation of dsRNAs. They highlight the mechanisms that prevent dsRNA sensors from binding to endogenous dsRNAs and activating innate immunity pathways. (Source: Molecular Cell)
Source: Molecular Cell - December 19, 2023 Category: Cytology Authors: Kyle A. Cottrell, Ryan J. Andrews, Brenda L. Bass Tags: Review Source Type: research

Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies
Chrustowicz, Sherpa, et  al. decipher evolutionarily conserved determinants of an exquisitely specific E3-E2 partnership ubiquitylating globular substrates. Cryo-EM visualizes a flexing GID E3 superassembly channeling its substrate between two ubiquitylation active sites. The catalytic architecture depends on multivalent Ubc8/UBE2H-GID/CTLH E3 contacts, including between multiphosphorylated E2 extensions and complementary E3 basic patches. (Source: Molecular Cell)
Source: Molecular Cell - December 18, 2023 Category: Cytology Authors: Jakub Chrustowicz, Dawafuti Sherpa, Jerry Li, Christine R. Langlois, Eleftheria C. Papadopoulou, D. Tung Vu, Laura A. Hehl, Özge Karayel, Viola Beier, Susanne von Gronau, Judith Müller, J. Rajan Prabu, Matthias Mann, Gary Kleiger, Arno F. Alpi, Brenda A Tags: Article Source Type: research

MORG1 limits mTORC1 signaling by inhibiting Rag GTPases
Abudu et  al. report that the WD-domain repeat protein MORG1 restricts mTORC1 signaling during nutrient-rich conditions, and this facilitates basal autophagy. MORG1 interacts with active Rag GTPases and inhibits the lysosomal recruitment of mTORC1. Moreover, MORG1 and p62/SQSTM1 act antagonistically on mTOR C1 activation upon amino acid withdrawal and restimulation. (Source: Molecular Cell)
Source: Molecular Cell - December 15, 2023 Category: Cytology Authors: Yakubu Princely Abudu, Athanasios Kournoutis, Hanne Britt Brenne, Trond Lamark, Terje Johansen Tags: Article Source Type: research

Ubiquiton —An inducible, linkage-specific polyubiquitylation tool
Analytical tools for investigating ubiquitin signaling are abundant, but methods to induce linkage-specific polyubiquitylation of a protein of interest have been missing. Renz et  al. have now developed rapamycin-inducible E3s specific for three major linkages and validated them for use in vitro in budding yeast and in mammalian cells. (Source: Molecular Cell)
Source: Molecular Cell - December 15, 2023 Category: Cytology Authors: Christian Renz, Evrydiki Asimaki, Cindy Meister, V éronique Albanèse, Kirill Petriukov, Nils C. Krapoth, Sabrina Wegmann, Hans-Peter Wollscheid, Ronald P. Wong, Amitkumar Fulzele, Jia-Xuan Chen, Sébastien Léon, Helle D. Ulrich Tags: Technology Source Type: research