Molecular Biology

Optogenetic control of Protein Kinase C-epsilon activity reveals its intrinsic signaling properties with spatiotemporal resolution

1. Qunxiang Ong
2. Crystal Jing Yi Lim
3. Yilie Liao
4. Justin Tze-Yang Ng
5. Ler Ting Rachel Lim
6. Shernys Xuan Yi Koh
7. Sher En Chan
8. Pheobe Lee Yu Ying
9. Huijun Lim
10. Chen Rui Ye
11. Loo Chien Wang
12. Siok Ghee Ler
13. Radoslaw M Sobota
14. Yaw Sing Tan
15. Gerald I Shulman
16. Xiaoyong Yang
17. Weiping Han

• Curated by eLife

  eLife Assessment

  This manuscript introduces Opto-PKCε, an optogenetic tool that enabled important findings derived from interactome and phosphoproteome studies. Light-dependent recruitment of Opto-PKCε to the plasma membrane revealed the specific phosphorylation of the insulin receptor at Thr 1160. In turn, recruitment to mitochondria led to phosphorylation of the complex I subunit NDUFS4, correlating with reduced spare respiratory capacity. The evidence supporting these conclusions is solid, although additional clarification on data analysis would further enhance readability.

Reviewed by eLife

tRNA synthetase activity is required for stress granule and P-body assembly

1. Max Baymiller
2. Noah S. Helton
3. Benjamin Dodd
4. Stephanie L. Moon

Reviewed by Life Science Editors Foundation

Acute Activation of Genes Through Transcriptional Condensates Impact Non-target Genes in a Chromatin Domain

1. Darshika Bohra
2. Zubairul Islam
3. Sundarraj Nidharshan
4. Aprotim Mazumder
5. Dimple Notani

• Curated by eLife

  eLife Assessment

  The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. These potentially important results suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, even though the estrogen responsive enhancer does not loop with the TFF3 promoter. To explain these results, the authors invoke a transcriptional condensate model. The claim of a temporal delay and effects of the target gene transcription on the non-target gene expression are supported by solid evidence but there is no direct evidence of the role of a condensate in mediating this effect. The reviewers appreciate that the authors have done a lot of work to strengthen the study. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

Reviewed by eLife

MagIC-Cryo-EM: Structural determination on magnetic beads for scarce macromolecules in heterogeneous samples

1. Yasuhiro Arimura
2. Hide A Konishi
3. Hironori Funabiki

• Curated by eLife

  eLife Assessment

  This study follows up on Arimura et al's powerful new method MagIC-Cryo-EM for imaging native complexes at high resolution. Using a clever design embedding protein spacers between the antibody and the nucleosomes purified, thereby minimizing interference from the beads, the authors concentrate linker histone variant H1.8 containing nucleosomes. From these samples, the authors obtain convincing atomic structures of the H1.8 bound chromatosome purified from interphase and metaphase cells, finding a NPM2 chaperone bound form exists as well. Caveats previously noted have been addressed nicely in the revision, strengthening the overall conclusions. This is an important new tool in the arsenal of single molecule biologists, permitting a deep dive into structure of native complexes, and will be of high interest to a broad swathe of scientists studying native macromolecules present at low concentrations in cells.

Reviewed by eLife

Transcriptomic meta-analysis in plaque psoriasis: an integrative bioinformatic approach to deciphering the genetic landscape and molecular pathways

1. Teresa Torres-Moral
2. Josep Riera-Monroig
3. Gemma Tell-Martí
4. Jaume Bagué
5. José F. Català-Senent
6. Francisco J. Roig
7. Míriam Potrony
8. Francisco García-García
9. Susana Puig

Reviewed by Arcadia Science

Small-molecule activation of TFEB alleviates Niemann–Pick disease type C via promoting lysosomal exocytosis and biogenesis

1. Kaili Du
2. Hongyu Chen
3. Zhaonan Pan
4. Mengli Zhao
5. Shixue Cheng
6. Yu Luo
7. Wenhe Zhang
8. Dan Li

• Curated by eLife

  eLife Assessment

  This study reports that activation of TFEB promotes lysosomal exocytosis and clearance of cholesterol from lysosomes, the strength of evidence for which is convincing with appropriate and validated methodology in line with current state-of-the-art. The significance of the findings is important in the context of Niemann-Pick Disease Type C as well as other subfields.

Reviewed by eLife

Changes in local mineral homeostasis facilitate the formation of benign and malignant testicular microcalcifications

1. Ida Marie Boisen
2. Nadia Krarup Knudsen
3. John Erik Nielsen
4. Ireen Kooij
5. Mathilde Louise Bagger
6. Jovana Kaludjerovic
7. Peter J O’ Shaughnessy
8. Peter W Andrews
9. Noriko Ide
10. Birgitte Grønkær Toft
11. Anders Juul
12. Arnela Mehmedbašić
13. Anne Jørgensen
14. Lee B Smith
15. Richard W Norman
16. Ewa Rajpert-De Meyts
17. Beate Lanske
18. Martin Blomberg Jensen

• Curated by eLife

  eLife Assessment

  This valuable study reports the link between a disruption in testicular mineral (phosphate) homeostasis, FGF23 expression, and Sertoli cell dysfunction. The data supporting the conclusion are solid. This work will be of interest to biomedical researchers working on testis biology and male infertility. The assessment is based on the editors' critical evaluation of the authors' responses.

Reviewed by eLife

Ubiquitin Ligase ITCH Regulates Life Cycle of SARS-CoV-2 Virus

1. Qiwang Xiang
2. Camille Wouters
3. Peixi Chang
4. Yu-Ning Lu
5. Mingming Liu
6. Haocheng Wang
7. Junqin Yang
8. Andrew Pekosz
9. Yanjin Zhang
10. Jiou Wang

• Curated by eLife

  eLife Assessment

  This study highlights ITCH as a regulator of SARS-CoV-2 replication by promoting K63-linked ubiquitination of M and E proteins. While the findings are potentially useful, the approaches are overly reliant on ectopic expression models and lack direct mechanistic evidence that ubiquitination of M and E has functional relevance. Accordingly, the strength of evidence is incomplete, as further experiments are needed to validate the findings and address potential confounding factors.

Reviewed by eLife

ORMDL3 restrains type I interferon signaling and anti-tumor immunity by promoting RIG-I degradation

1. Qi Zeng
2. Chen Yao
3. Shimeng Zhang
4. Yizhi Mao
5. Jing Wang
6. Ziyang Wang
7. Chunjie Sheng
8. Shuai Chen

• Curated by eLife

  eLife Assessment

  This study provides important insights into the regulation of type-I interferon signaling and anti-tumor immunity, demonstrating that ORMDL3 promotes RIG-I degradation to suppress immune responses. The evidence is convincing, with well-executed mechanistic experiments and in vivo validation in syngeneic tumor models. These findings have significant implications for cancer immunotherapy, highlighting ORMDL3 as a potential therapeutic target.

Reviewed by eLife

Insufficiency of 40S ribosomal proteins, RPS26 and RPS25, negatively affects biosynthesis of polyglycine-containing proteins in fragile-X associated conditions

1. Katarzyna Tutak
2. Izabela Broniarek
3. Andrzej Zielezinski
4. Daria Niewiadomska
5. Tomasz Skrzypczak
6. Anna Baud
7. Krzysztof Sobczak

• Curated by eLife

  eLife Assessment

  In this valuable study, Tutak and colleagues set out to identify factors that mediate Repeat Associated Non-AUG (RAN) translation of CGG repeats in the FMR1 mRNA which are implicated in toxic protein accumulation that underpins ensuing neurological pathologies. The authors provide solid evidence that RPS26 may be implicated in mediating the RAN translation of FMR1 mRNA. This article should be of broad interest to researchers in the variety of disciplines including post-transcriptional regulation of gene expression and neurobiology.

Reviewed by eLife