Molecular Biology

RNase III cleavage signals spread across splice junctions enforce sequential processing of co-hosted snoRNAs

1. Valérie Migeot
2. Yves Mary
3. Etienne Fafard-Couture
4. Pierre Lombard
5. François Bachand
6. Michelle S Scott
7. Carlo Yague-Sanz

Reviewed by Review Commons

Negative regulation of miRNAs sorting in EVs: the RNA-binding protein PCBP2 impairs SYNCRIP-mediated miRNAs EVs loading

1. Francesco Marocco
2. Sabrina Garbo
3. Claudia Montaldo
4. Alessio Colantoni
5. Luca Quattrocchi
6. Gioele Gaboardi
7. Giovanna Sabarese
8. Carla Cicchini
9. Mario Lecce
10. Alessia Carnevale
11. Rossella Paolini
12. Gian Gaetano Tartaglia
13. Cecilia Battistelli
14. Marco Tripodi

• Curated by eLife

  eLife Assessment

  This manuscript makes a valuable contribution to the field by uncovering a molecular mechanism for miRNA intracellular retention, mediated by the interaction of PCBP2, SYNCRIP, and specific miRNA motifs. The findings are convincing and advance our understanding of RNA-binding protein-mediated miRNA sorting, providing deeper insights into miRNA dynamics.

Reviewed by eLife

Structure of an oxygen-induced tubular nanocompartment in Pyrococcus furiosus

1. Wenfei Song
2. Jan Fiala
3. Ioannis Skalidis
4. Pascal Albanese
5. Constantinos Patinios
6. Marten L Chaillet
7. Servé WM Kengen
8. Richard A Scheltema
9. Stuart C Howes
10. Albert JR Heck
11. Friedrich Förster

• Curated by eLife

  eLife Assessment

  Using advanced CryoEM and mass spectrometry, the authors provide compelling evidence of how tubule formation occurs in an oxygen-dependent manner. These fundamental findings offer a novel mechanism by which rubrerythrin tubules encapsulate encapsulin to prevent oxidative stress in Pyrococcus furiosus. However, there are a few reasonable concerns about biochemical validations and the lack of adequate description of results and methodology.

Reviewed by eLife

Synonymous mutations in AAV Rep enhance genome packaging in a library selection

1. Tasfia Azim
2. Dru Myerscough
3. Jonathan J Silberg

• Curated by eLife

  eLife Assessment

  Engineering of adeno-associated virus (AAV) replication proteins may provide new insights into Parvoviral replication. The authors created a useful collection of Rep protein variants with changes that alter the amino acid sequence, but these did not lead to clear improvements in how the virus worked. Instead, their screen showed that changes that do not alter the protein ("synonymous" mutations) and changes to the promoter were more common. As it stands the results are incomplete due to potential issues with the screening design. We encourage a more complete characterization, which may enhance the translational potential of the approach.

Reviewed by eLife

PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification

1. José Antonio Valer
2. Alexandre Deber
3. Marius Wits
4. Carolina Pimenta-Lopes
5. Marie-José Goumans
6. José Luis Rosa
7. Gonzalo Sánchez-Duffhues
8. Francesc Ventura

• Curated by eLife

  eLife Assessment

  This study, which includes additional experiments in response to the reviewer comments, presents valuable findings illustrating the role of PI3Kα in heterotopic ossification in FOP model mice. The methods, data, and analyses are solid and generally support the claims although as noted by one of the reviewers, there is no data demonstrating the effect of BYL79 on cell growth, and it remains unclear whether BYL79 also inhibits the Smad2/3 pathway. While this study provides new insights into the role of the PI3Kα pathway as a therapeutic target for FOP, questions about the mechanism of BYL79 still exist.

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 work will be of interest to the community of homologous recombination and DNA repair, as well as genome stability more generally.

Reviewed by eLife

The Viral AlphaFold Database of monomers and homodimers reveals conserved protein folds in viruses of bacteria, archaea, and eukaryotes

1. Roni Odai
2. Michèle Leemann
3. Tamim Al-Murad
4. Minhal Abdullah
5. Lena Shyrokova
6. Tanel Tenson
7. Vasili Hauryliuk
8. Janani Durairaj
9. Joana Pereira
10. Gemma C. Atkinson

Reviewed by Arcadia Science

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 preLights, Life Science Editors Foundation

Nuclear and cytosolic J-domain proteins provide synergistic control of Hsf1 at distinct phases of the heat shock response

1. Carmen Ruger-Herreros
2. Lucia Svoboda
3. Gurranna Male
4. Aseem Shrivastava
5. Markus Höpfler
6. Katharina Jetzinger
7. Jiri Koubek
8. Günter Kramer
9. Fabian den Brave
10. Axel Mogk
11. David S Gross
12. Bernd Bukau

• Curated by eLife

  eLife Assessment

  This valuable study focuses on defining how the HSP70 chaperone system utilizes J-domain proteins to regulate the heat shock response-associated transcription factor HSF1. Using a combination of orthogonal techniques in yeast, this manuscript provides compelling evidence that the J-domain protein Apj1 facilitates attenuation of HSF1 transcriptional activity through a mechanism involving its dissociation from heat shock gene promoter regions. This work improves our understanding of HSF1 regulation and will be of broad interest to cell biologists interested in proteostasis, chaperone networks, and stress-responsive signaling.

Reviewed by eLife

Conserved and Unique Features of Terminal Telomeric Sequences in ALT-Positive Cancer Cells

1. Benura Azeroglu
2. Wei Wu
3. Raphael Pavani
4. Ranjodh 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 genome-wide 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, the new insights are fundamental and compelling, and the optimized END-seq approaches will be widely utilized. The interest of the paper could be heightened by deepening the discussion of potential biases in telomere representation, the origin of the ssDNA captured in ALT cells, and the occurrence of variant telomere repeats in the cell lines studied.

Reviewed by eLife