Molecular Biology

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

Maf-family bZIP transcription factor NRL interacts with RNA-binding proteins and R-loops in retinal photoreceptors

1. Ximena Corso Diaz
2. Xulong Liang
3. Kiam Preston
4. Bilguun Tegshee
5. Milton A English
6. Jacob Nellissery
7. Sharda Prasad Yadav
8. Claire Marchal
9. Anand Swaroop

• Curated by eLife

  eLife Assessment

  This important study employed multiple orthogonal techniques and tissue samples to investigate the interaction between the NRL transcription factor and RNA-binding proteins in the retina. The findings are convincing to support an interaction between NRL and the DHX9 helicase. The significance of the study could be enhanced with functional experiments of NRL-R-loop interactions in the developing retina and their potential role in photoreceptor health and gene regulation.

Reviewed by eLife

The SUMO activating enzyme subunit, SAE2, contributes SUMO protein bias for mitotic fidelity

1. Alexandra K. Walker
2. Alexander J. Lanz
3. Mohammed Jamshad
4. Alexander J. Garvin
5. Peter Wotherspoon
6. Benjamin F. Cooper
7. Timothy J. Knowles
8. Joanna R. Morris

Reviewed by Review Commons

Improved base editing and functional screening in Leishmania via co-expression of the AsCas12a ultra variant, a T7 RNA polymerase, and a cytosine base editor

1. Nicole Herrmann May
2. Anh Cao
3. Annika Schmid
4. Fabian Link
5. Jorge Arias-del-Angel
6. Elisabeth Meiser
7. Tom Beneke

• Curated by eLife

  eLife Assessment

  This important article describes a meticulously-developed improved strategy for generation of functionally null mutants in Leishmania spp. via cytosine base editing, with reduced background toxicity and enhanced efficiency relative to a previously-described method. The authors show use of the strategy in a small-scale loss-of-function screen, providing compelling evidence that large-scale screens will be possible. The newly developed tools will be of great interest to researchers working with Leishmania and beyond.

Reviewed by eLife

Embryological cellular origins and hypoxia-mediated mechanisms in PIK3CA -Driven refractory vascular malformations

1. Sota Torii
2. Keiki Nagaharu
3. Nanako Nakanishi
4. Hidehito Usui
5. Yumiko Hori
6. Katsutoshi Hirose
7. Satoru Toyosawa
8. Eiichi Morii
9. Mitsunaga Narushima
10. Yoshiaki Kubota
11. Osamu Nakagawa
12. Kyoko Imanaka-Yoshida
13. Kazuaki Maruyama

Reviewed by Review Commons

A transcriptional control model for doublesex -dependent sex differentiation in Nasonia wasps

1. Julien Rougeot
2. Filippo Guerra
3. Eveline C. Verhulst

Reviewed by Arcadia Science

Sperm fertility in mice with oligo-astheno-teratozoospermia restored by in vivo injection and electroporation of naked mRNA

1. Charline Vilpreux
2. Guillaume Martinez
3. Paul Fourquin
4. Magali Court
5. Florence Appaix
6. Jean-Luc Duteyrat
7. Maxime Henry
8. Julien Vollaire
9. Camille Ayad
10. Altan Yavuz
11. Lisa De Macedo
12. Geneviève Chevalier
13. Edgar Del Llano
14. Emeline Lambert
15. Sekou Ahmed Conte
16. Zeina Wehbe
17. Elsa Giordani
18. Véronique Josserand
19. Jacques Brocard
20. Coutton Charles
21. Bernard Verrier
22. Pierre F Ray
23. Corinne Loeuillet
24. Christophe Arnoult
25. Jessica Escoffier

• Curated by eLife

  eLife Assessment

  This study reports an approach for restoring sperm motility in mice. The strength lies in in the novelty of the methodology being developed, but the evidence for the success of the method or its mechanism is inadequate. Additional experimental support would be required to support the conclusions of the authors.

Reviewed by eLife

Conformational changes, excess area, and elasticity of the Piezo protein-membrane nanodome from coarse-grained and atomistic simulations

1. Sneha Dixit
2. Frank Noé
3. Thomas R. Weikl

• Curated by eLife

  eLife Assessment

  This work represents an important contribution to our understanding of how membrane energetics influence protein conformation and function in mechano-sensitive channels. Through extensive molecular dynamics simulations and energetic analysis, the study demonstrates how the channel structure is shaped by a balance of protein and membrane-induced forces, effectively reconciling experimental data from different membrane environments. However, while much of the computational data is convincing, some aspects of the energetic analysis and models employed remain incomplete.

Reviewed by eLife

N6-methyladenosine in DNA promotes genome stability

1. Brooke A Conti
2. Leo Novikov
3. Deyan Tong
4. Qing Xiang
5. Savon Vigil
6. Thomas J McLellan
7. Chuong Nguyen
8. Nancy De La Cruz
9. Reshma T Veettil
10. Prashant Pradhan
11. Parag Sahasrabudhe
12. Jason D Arroyo
13. Lei Shang
14. Benjamin R Sabari
15. David J Shields
16. Mariano Oppikofer

• Curated by eLife

  eLife Assessment

  This manuscript reports important findings that the methyltransferase METTL3 is involved in the repair of abasic sites and uracil in DNA, mediating resistance to floxuridine-driven cytotoxicity. The presented evidence is conclusive for the involvement of m6A in DNA involving single cell imaging and mass spectrometry data. The authors present convincing evidence that the m6A signal does not result from bacterial contamination or RNA.

Reviewed by eLife