Molecular Biology

Distinct Mechanisms for Inhibition of SARS-CoV-2 Main Protease: Dimerization Promoted by Peptidomimetic Inhibitors and Disrupted by Ebselen

1. Chengxi Liu
2. Qinyu Jia
3. Chang Zhao
4. Zhong-Ping Yao

• Curated by eLife

  eLife Assessment

  This important study provides a comprehensive comparison of the mechanisms through which different inhibitors affect the SARS-CoV-2 main protease, a pivotal antiviral drug target, and suggests a potentially broad-spectrum strategy to inhibit this critical viral enzyme by disrupting its dimerization states. However, whereas the biophysical analyses of the dimer stability are convincing, evidence supporting this new mode of mechanism to inhibit the main protease is incomplete and would benefit from a correlation of the biophysical observations with functional activity. With the functional validation part strengthened, this work would be of interest to biochemists and virologists working on anti-coronavirus drug discovery.

Reviewed by eLife

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

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

• Curated by eLife

  eLife Assessment

  This study reports an mRNA-based strategy for restoring sperm motility in a mouse model of monogenic male infertility. The work is technically innovative and potentially valuable, as it demonstrates feasibility of in vivo testicular mRNA delivery without genomic integration of foreign DNA. However, although partial recovery of sperm motility is supported, the evidence for meaningful restoration of fertility remains incomplete, with weak IVF outcomes and difficult-to-interpret ICSI results. In addition, mechanistic questions regarding the persistence of mRNA and the specificity of germ-cell targeting remain insufficiently resolved, limiting the strength of the authors' conclusions.

Reviewed by eLife

EPB41L4A-AS1 long noncoding RNA acts in both cis- and trans-acting transcriptional regulation and controls nucleolar biology

1. Alan Monziani
2. Juan Pablo Unfried
3. Todor Cvetanovic
4. Igor Ulitsky

• Curated by eLife

  eLife Assessment

  This paper provides important findings towards understanding the role of the lncRNA EPB41L4A-AS1 in a human cell line. The data is generally convincing, supported by extensive and clever integrative analysis. The work provides insights into how this lncRNA regulates gene expression via complex mechanisms; however the biological relevance awaits validation in other models.

Reviewed by eLife

FRG1 Regulates Nonsense-Mediated mRNA Decay by Modulating UPF1 Levels

1. Ananya Palo
2. Talina Mohapatra
3. Anamika Singh
4. Shithij Thalakkat
5. Suryasikha Mohanty
6. Rajeeb Kumar Swain
7. Manjusha Dixit

• Curated by eLife

  eLife Assessment

  This useful study by Palo et al proposes that FRG1 functions as a negative regulator of Nonsense-Mediated mRNA decay (NMD) by associating with the exon junction complex (EJC) and destabilizing UPF1 independently of DUX4. The authors present solid evidence to dissect the relationship between FRG1 and DUX4 in NMD. However, the evidence to support the claim that FRG1 is a component of the EJC or the NMD machinery is incomplete.

Reviewed by eLife

Specialization of ubiquitin ligases to distinct nucleic acid sensors

1. Ibrahim Syed
2. Sheng Chen
3. David J. Peeler
4. Paul F. McKay
5. Marco A. Briones-Orta
6. Jennifer A. Bohn
7. Robin J. Shattock
8. Daniel Gonçalves-Carneiro

Reviewed by Review Commons

The chromatin remodeller CHD4 regulates transcription factor binding to both prevent activation of silent enhancers and maintain active regulatory elements

1. Andria Koulle
2. Oluwaseun Ogundele
3. Devina Shah
4. India Baker
5. Maya Lopez
6. David Lando
7. Nicola Reynolds
8. Ramy Ragheb
9. Ernest D Laue
10. Brian Hendrich

• Curated by eLife

  eLife Assessment

  This work offers important insights into the protein CHD4's function in chromatin remodeling and gene regulation in embryonic stem cells, supported by extensive biochemical, genomic, and imaging data. The use of an inducible degron system allows precise functional analysis, and the datasets generated represent a key resource for the field. The revised study offers compelling evidence and makes a significant contribution to understanding CHD4's role in epigenetic regulation. This work will be of interest to the epigenetics and stem biology fields.

Reviewed by eLife

A novel high-throughput single-cell DNA sequencing method reveals hidden genomic heterogeneity in the unicellular eukaryote Leishmania

1. Gabriel H Negreira
2. Pieter Monsieurs
3. Jean-Claude Dujardin
4. Malgorzata A Domagalska

• Curated by eLife

  eLife Assessment

  This important study, which tackles the challenge of analyzing genome integrity and instability in unicellular pathogens by introducing a novel single-cell genomics approach, presents compelling evidence that this new tool outperforms standard whole-genome amplification techniques. While thorough and rigorous, the work's impact would increase by providing scripts and data, as well as a description of the biological relevance that would make this method more appealing to the broad community studying genetic heterogeneity in diverse organisms.

Reviewed by eLife

HP1β and H3K9me3 Regulate Olfactory Receptor Choice and Transcriptional Identity

1. Martín Escamilla-del-Arenal
2. Rachel Duffié
3. Hani Shayya
4. Valentina Loconte
5. Axel Ekman
6. Lena Annika Street
7. Adan Horta
8. Daniele Canzio
9. Kevin Monahan
10. Carolyn Larabell
11. Marko Jovanovic
12. Stavros Lomvardas

Reviewed by PREreview

Translational response to mitochondrial stresses is orchestrated by tRNA modifications

1. Sherif Rashad
2. Shadi Al-Mesitef
3. Abdulrahman Mousa
4. Yuan Zhou
5. Daisuke Ando
6. Guangxin Sun
7. Tomoko Fukuuchi
8. Yuko Iwasaki
9. Jingdong Xiang
10. Shane R Byrne
11. Jingjing Sun
12. Masamitsu Maekawa
13. Daisuke Saigusa
14. Thomas J Begley
15. Peter C Dedon
16. Kuniyasu Niizuma

Reviewed by PREreview

Development of Loop Mediated Isothermal Amplification for Rapid and Sensitive Detection of Enteroaggregative Escherichia coli (EAEC)

1. Alazar Amare Amdiyee
2. Tesfaye Sisay Tessema

Reviewed by PREreview