Molecular Biology

Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells

1. Mykola Roiuk
2. Marilena Neff
3. Aurelio A Teleman

• Curated by eLife

  eLife Assessment

  In this valuable study, Roiuk et al combined ribosome profiling and reporter assays to provide compelling evidence that eIF2A does not have a major impact on mRNA translation in HeLa cells. These findings are consistent with several recent publications that disaffirm the previously proposed role of eIF2A in directing protein synthesis under stress. Considering that stress-dependent perturbations in translation play a major role in homeostasis and several pathological states (e.g., cancer and neurological disorders), this work should be of broad interest to researchers studying regulation of gene expression, stress-adaptation, cancer and neurobiology.

Reviewed by eLife

The molecular logic of Gtr1/2- and Pib2-dependent TORC1 regulation in budding yeast

1. Jacob H Cecil
2. Cristina M Padilla
3. Austin A Lipinski
4. Paul Langlais
5. Xiangxia Luo
6. Andrew P Capaldi

• Curated by eLife

  eLife assessment

  The study presents valuable findings concerning how a highly conserved signal transduction pathway helps budding yeast cells adapt their growth to nitrogen sources of differing qualities. However, the evidence is incomplete for the authors' main claim that the pathway adopts three distinct states depending on the nitrogen source. The presented data, particularly phospho-proteomic datasets, will be of interest to the cell growth signaling community.

Reviewed by eLife

Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels

1. Veronica Cherdyntseva
2. Joanna Paulson
3. Selin Adakli
4. Jean-Philippe Gagné
5. Moses Aouami
6. Patricia Ubieto-Capella
7. Daniel González-Acosta
8. Collin Bakker
9. Guy G. Poirier
10. Nitika Taneja
11. Massimo Lopes

Reviewed by preLights

NF- _κ B is a Central Regulator of Hypoxia-Induced Gene Expression

1. Dilem Shakir
2. Michael Batie
3. Chun-Sui Kwok
4. Simon J. Cook
5. Niall S. Kenneth
6. Sonia Rocha

Reviewed by Review Commons

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 miRNA sorting into EVs is mediated by the capacity of RBP PCBP2 to impair the SYNCRIP-dependent miRNA 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-Lope
5. Marie-José Goumans
6. Jose 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

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