Molecular Biology

A TranSNP in the DDIT4 mRNA can impact its translation efficiency and modulate p53-dependent responses in cancer cells

1. Meriem Hadjer Hamadou
2. Laura Alunno
3. Tecla Venturelli
4. Samuel Valentini
5. Davide Dalfovo
6. Francesca Lorenzini
7. Alessia Mattivi
8. Vincenza Vigorito
9. Glenda Paola Grupelli
10. Alessandro Matte’
11. Pamela Gatto
12. Michael Pancher
13. Chiara Valentini
14. Veronica De Sanctis
15. Roberto Bertorelli
16. Virginie Marcel
17. Emilio Cusanelli
18. Stefano Freddi
19. Giovanni Bertalot
20. Sara Zaccara
21. Marina Mione
22. Luca L. Fava
23. Alessandro Romanel
24. Alberto Inga

Reviewed by Review Commons

Single-cell proteomics workflow for characterizing heterogeneous cell populations in saliva and tear fluid

1. Jackson Gabriel Miyamoto
2. Heloísa Monteiro do Amaral-Prado
3. Fábio Malta de Sá Patroni
4. Guilherme Pimentel Telles
5. Carolina Moretto Carnielli
6. Guilherme Araújo Câmara
7. Daniella de Figueiredo
8. Elaine Cristina Cardoso
9. Daniela Campos Granato
10. Alan Roger Santos-Silva
11. Marcio Ajudarte Lopes
12. Adriana Franco Paes Leme

Reviewed by PREreview

Deletion of sulfate transporter SUL1 extends yeast replicative lifespan via reduced PKA signaling instead of decreased sulfate uptake

1. Juan Long
2. Meng Ma
3. Yuting Chen
4. Bo Gong
5. Yi Zheng
6. Hao Li
7. Jing Yang

• Curated by eLife

  eLife Assessment

  This study offers a valuable contribution to the understanding of how inorganic nutrient transporters, particularly SUL1, influence yeast lifespan through signaling pathways rather than transport functions. The findings suggest a novel link between SUL1 deletion and extended replicative lifespan, supported by transcriptomic and stress-response data. However, the strength of the evidence remains incomplete, with key experiments-such as sulfate supplementation tests, functional autophagy validation, and transport assays-either missing or insufficiently described. As a result, while the manuscript presents promising insights, additional work is needed to robustly support its conclusions.

Reviewed by eLife

An aphid-resistant plant metabolite as a candidate aphicide: Insight into the bioactivity and action mode of betulin against aphids

1. Junxiu Wang
2. Matthana Klakong
3. Qiuyu Zhu
4. Jinting Pan
5. Yudie Duan
6. Lirong Wang
7. Yong Li
8. Jiangbo Dang
9. Danlong Jing
10. Hong Zhou

• Curated by eLife

  eLife Assessment

  This study presents important findings on the insecticidal mechanism of betulin, a plant-derived metabolite, in controlling the aphid Myzus persicae and it provides a demonstration that betulin targets the GABA receptor in aphids, with strong supporting evidence from transcriptomic, biochemical, electrophysiological, and genetic approaches. In particular, the identification of a specific conserved residue (THR228) critical for betulin binding advances our understanding of insect neuropharmacology and offers translational potential for pest management strategies. The evidence supporting the primary claims is solid, with well-integrated methodologies and appropriate controls; however, some interpretative and methodological limitations remain, including the option to further explore off-target effects, as well as the broader evolutionary and ecological context. Addressing these points would strengthen the broader implications of the study.

Reviewed by eLife

Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation

1. Freya Storer
2. Colin D. McClure
3. Alicia Estacio Gomez
4. Tsz Lam Wong
5. Lucy J. Minkley
6. Tony D. Southall

Reviewed by Review Commons

Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells

1. Benura Azeroglu
2. Wei Wu
3. Raphael Pavani
4. Ranjodh Singh Sandhu
5. Tadahiko Matsumoto
6. André Nussenzweig
7. Eros Lazzerini-Denchi

• Curated by eLife

  eLife Assessment

  This study demonstrates the application of END-seq, originally developed to study genomewide DNA double-strand breaks, to telomere biology; the work packs a punch, concisely demonstrating the utility of this approach and the new insights that can be gained. The authors confirm that telomeres in telomerase-positive cells terminate with 5'-ATC in a Pot1-dependent manner, and demonstrate that this principle holds true in telomerase-negative ALT cells as well. S1-END-seq is similarly developed for telomeres, showing that ALT cells harbor several regions of ssDNA. The study is well-executed and convincing, the new insights are fundamental and compelling, and the optimized END-seq approaches will be widely utilized. The work will prompt additional studies that the reviewers look forward to, including combining telomeric END-seq with long-read sequencing to address the distribution and origin of variant telomere repeats and ssDNA along telomeres in ALT and telomerase-positive settings.

Reviewed by eLife

Structural mechanism of strand exchange by the RAD51 filament

1. Luay Joudeh
2. Robert E Appleby
3. Joseph D Maman
4. Luca Pellegrini

• Curated by eLife

  eLife Assessment

  This landmark study describes the structure of the human RAD51 filament with a recombination intermediate called the displacement loop (D-loop). Using cryogenic structural, biochemical, and single-molecule analyses, the authors provide compelling evidence on how the RAD51 filament promotes strand exchange between single-stranded and double-stranded DNAs. The findings are highly relevant to the fields of homologous recombination, DNA repair, and genome stability.

Reviewed by eLife

Single-cell profiling of trabecular meshwork identifies mitochondrial dysfunction in a glaucoma model that is protected by vitamin B3 treatment

1. Nicholas Tolman
2. Taibo Li
3. Revathi Balasubramanian
4. Guorong Li
5. Violet Bupp-Chickering
6. Ruth A Kelly
7. Marina Simón
8. John Peregrin
9. Christa Montgomery
10. W Daniel Stamer
11. Jiang Qian
12. Simon WM John

• Curated by eLife

  eLife Assessment

  This is a fundamental study that provides a detailed single-cell transcriptomic and epigenomic map of the mouse trabecular meshwor, identifying three distinct trabecular meshwor subtypes with specific functional roles. It links the glaucoma-associated transcription factor LMX1B to mitochondrial regulation in TM3 cells and demonstrates that nicotinamide treatment prevents IOP elevation in Lmx1bV265D/+ mutant mice, highlighting a potential metabolic therapeutic strategy for glaucoma. This convincing work would be further supported by data that link the transcriptional data with mitochondrial functional assays.

Reviewed by eLife

Insights from aquaporin structures into drug-resistant sleeping sickness

1. Modestas Matusevicius
2. Robin A Corey
3. Marcos Gragera
4. Keitaro Yamashita
5. Teresa Sprenger
6. Marzuq A Ungogo
7. James N Blaza
8. Pablo Castro-Hartmann
9. Dimitri Y Chirgadze
10. Sundeep Chaitanya Vedithi
11. Pavel Afanasyev
12. Roberto Melero
13. Rangana Warshamanage
14. Anastasiia Gusach
15. Jose Maria Carazo
16. Mark Carrington
17. Tom L Blundell
18. Garib Murshudov
19. Phillip Stansfeld
20. Mark Sansom
21. Harry P de Koning
22. Christopher G Tate
23. Simone N Weyand

• Curated by eLife

  eLife Assessment

  In this important study, the authors set out to determine the molecular interactions between the AQP2 from Trypanosoma brucei (TbAQP2) and the trypanocidal drugs pentamidine and melarsoprol in order to clarify the origins of clinically observed drug resistance and facilitate future drug design. Using cryo-EM, molecular dynamics simulations, and lysis assays, the authors present a solid theory for how drug resistance mutations in TbAQP2 prevent drug uptake. Overall, even though a few methodological issues still need minor clarification, this study will be of interest to those working on aquaporins and the development of drugs targeting aquaporins.

Reviewed by eLife

Molecular Landscape of the Mouse Adrenal Gland and Adjacent Adipose by Spatial Transcriptomics

1. Małgorzata Blatkiewicz
2. Szymon Hryhorowicz
3. Marta Szyszka
4. Joanna Suszyńska-Zajczyk
5. Andrzej Pławski
6. Adam Plewiński
7. Andrea Porzionato
8. Ludwik K Malendowicz
9. Marcin Rucinski

• Curated by eLife

  eLife Assessment

  This useful study provides a spatial transcriptomic analysis of the mouse adrenal gland that could have implications for future research and applications. The authors present solid results that allow the dissection of the cell signalling pathways and cellular composition of different zones of the adrenal glands in the mouse model; they propose new zone-specific gene markers and specific intra- and inter-zonal signaling pathways based on receptor-ligand expression patterns. Their web tool is user-friendly and will be helpful for adrenal scientists; however, the validation of crucial results of the large dataset is necessary. There are also several contradictory results/interpretations, and the opportunity to dissect the sexually dimorphic gene expression pattern and mouse-human interspecies differences is a missed opportunity.

Reviewed by eLife