Molecular Biology

Protein secretion routes in fungi are mostly determined by the length of the hydrophobic helix in the signal peptide

1. Tristan Sones-Dykes
2. Edward Wallace

Reviewed by Review Commons

The spike tip protein of bacteriophage T4

1. Yves Mattenberger
2. Ekaterina S Knyazhanskaya
3. Mikhail M Shneider
4. Sergey A Buth
5. Sergey Nazarov
6. William P Robins
7. Petr G Leiman
8. Dominique Belin

• Curated by eLife

  eLife Assessment

  This important study by Mattenburger et al. employs structural biology, biochemistry, and genetics to advance understanding of how bacteriophage contractile injection systems mediate host recognition and DNA delivery, yielding a remarkable 1.15 A crystal structure of the T4 spike tip complex (gp5-gp5.4). The compelling evidence presented demonstrates that the spike tip protein gp5.4 is essential for phage fitness and successful infection of Escherichia coli strains bearing truncated lipopolysaccharide; however, direct proof regarding interaction with the cell wall or its components is lacking. The study further provides biochemical evidence that the analogous spike tip protein from phage P2 (GpV) is translocated into the host periplasm during infection, together establishing the spike tip as a critical and active component of the phage infection machinery.

Reviewed by eLife

Systematic analysis of network-driven adaptive resistance to CDK4/6 and oestrogen receptor inhibition using meta-dynamic network modelling

1. Anthony Hart
2. Sung-Young Shin
3. Lan K Nguyen

• Curated by eLife

  eLife Assessment

  This manuscript presents a useful computational framework for systematically characterising how heterogeneity in initial conditions or biophysical parameters shapes the dynamic behaviour of protein signalling networks, with potential relevance to understanding adaptive drug resistance. While the approach represents a significant methodological contribution, the extent to which its conclusions are biologically informative remains debated, as the model is only qualitatively compared with experimental data and lacks quantitative validation. As a result, the strength of evidence supporting the mechanistic claims is viewed as incomplete.

Reviewed by eLife

Uncovering shared and tissue-specific molecular adaptations to intermittent fasting in liver, brain, and muscle

1. Yibo Fan
2. Senuri De Silva
3. Nishat I Tabassum
4. Xiangyuan Peng
5. Vernise JT Lim
6. Xiangru Cheng
7. Keshava K Datta
8. Rohan Lowe
9. Terrance G Johns
10. Mark P Mattson
11. Suresh Mathivanan
12. Christopher G Sobey
13. Eitan Okun
14. Yong U Liu
15. Guobing Chen
16. Mitchell Kim Peng Lai
17. Dong-Gyu Jo
18. Jayantha Gunaratne
19. Thiruma V Arumugam

• Curated by eLife

  eLife Assessment

  This is a solid paper on intermittent fasting that will be of interest to readers. The data presented are certainly valuable as a resource. The findings of both shared and tissue-specific signatures, both at the proteomic and transcriptomic levels, align well with what has been established and bring new insight into metabolic adaptation and its consequences in muscle, cortex, and liver. The organ specific changes unveiled by proteomics in response to IF reveal unique rewiring of metabolic, signaling and physiological function.

Reviewed by eLife

Structural basis for the folding of PINK1 by the HSP90–CDC37 chaperone complex

1. Kei Okatsu
2. Hayato Yamamoto
3. Akinori Okamoto
4. Shinya H Goto
5. Yumiko Nishimoto
6. Yukihiko Sugita
7. Takeshi Noda
8. Shuya Fukai

• Curated by eLife

  eLife Assessment

  This study presents a high-quality cryo-EM structure of the human kinase PINK1 in complex with the HSP90-CDC37 chaperone complex, capturing a partially folded intermediate in which the C-lobe and C-terminal extension are structured while the N-lobe remains unfolded and engaged by the HSP90 clamp. The structural data are broadly consistent with a recently published structure of the same complex, providing useful insight into early steps of PINK1 maturation and highlighting residues linked to familial Parkinson's disease. However, the mechanistic conclusions remain incomplete because the manuscript does not experimentally validate key hypotheses raised by the structure, including the functional roles of the C-lobe interface, the HPNI motif, the C-terminal extension, or the proposed competition between HSP90 and TOM20.

Reviewed by eLife

Global molecular landscape of early MASLD progression in human obesity

1. Qing Zhao
2. William De Nardo
3. Ruoyu Wang
4. Yi Zhong
5. Umur Keles
6. Gabriele Sakalauskaite
7. Li Na Zhao
8. Huiyi Tay
9. Sonia Youhanna
10. Mengchao Yan
11. Ye Xie
12. Youngrae Kim
13. Sungdong Lee
14. Rachel Liyu Lim
15. Guoshou Teo
16. Pradeep Narayanaswamy
17. Paul R Burton
18. Volker M Lauschke
19. Hyungwon Choi
20. Matthew J Watt
21. Philipp Kaldis

• Curated by eLife

  eLife Assessment

  The authors provide a useful resource and approach to identify early-stage biomarkers of MASLD progression, notably when no other apparent symptoms have arisen. The strength of evidence to support new MASLD signatures is solid as the work combines metabolomic and transcriptomic measures in blood and liver biopsies.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

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