Molecular Biology

Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury

1. Lilija Wehling
2. Liam Keegan
3. Paula Fernández-Palanca
4. Reham Hassan
5. Ahmed Ghallab
6. Jennifer Schmitt
7. Yingyue Tang
8. Maxime Le Marois
9. Stephanie Roessler
10. Peter Schirmacher
11. Ursula Kummer
12. Jan G Hengstler
13. Sven Sahle
14. Kai Breuhahn

• Curated by eLife

  Evaluation Summary:

  The authors made an important extension of the canonical Hippo pathway by showing that nuclear phosphorylation of the pathway components YAP/TAZ contributes to the shuttling between different cellular compartments. The conclusions are well supported by the experimental evidence under both physiological and tissue-damaging conditions. Given the importance and developmental conserveness of the Hippo pathway, the work is of broad interest to the field of developmental and regenerative biology.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Unleashing a novel function of Endonuclease G in mitochondrial genome instability

1. Sumedha Dahal
2. Humaira Siddiqua
3. Shivangi Sharma
4. Ravi K Babu
5. Diksha Rathore
6. Sheetal Sharma
7. Sathees C Raghavan

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest for researchers in the field of mitochondrial genome stability and mitochondrial genetic diseases. The authors show that endonuclease G preferentially binds to mitochondrial genome regions which have a potential for forming G4 tetraplexes, inducing DNA breaks that may lead to a common 9 bp deletion in the mitochondrial genome by microhomology-mediated endjoining.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility

1. Margalida Torrens-Mas
2. Catalina M Perelló-Reus
3. Neus Trias-Ferrer
4. Lesly Ibargüen-González
5. Catalina Crespí
6. Aina Maria Galmes-Panades
7. Cayetano Navas-Enamorado
8. Andres Sanchez-Polo
9. Javier Piérola-Lopetegui
10. Luis Masmiquel
11. Lorenzo Socias Crespi
12. Carles Barcelo
13. Marta Gonzalez-Freire

Reviewed by ScreenIT

A new insight into RecA filament regulation by RecX from the analysis of conformation-specific interactions

1. Aleksandr Alekseev
2. Georgii Pobegalov
3. Natalia Morozova
4. Alexey Vedyaykin
5. Galina Cherevatenko
6. Alexander Yakimov
7. Dmitry Baitin
8. Mikhail Khodorkovskii

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to readers in the fields of DNA repair, DNA-protein interactions and those employing single-molecule techniques. Using single-molecule methods, the authors discovered that RecX exerts its regulatory effect on the RecA filament through two modes of action: i) by promoting RecA dissociation from ssDNA, and ii) by causing a reversible conformational change of the filament. The latter mode of RecX action is novel and of particular interest. The authors present a plausible model of the RecX-RecA-ATP-ssDNA system that could be further validated in future experiments.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Mouse nuclear RNAi-defective 2 promotes splicing of weak 5′ splice sites

1. Matyas Flemr
2. Michaela Schwaiger
3. Daniel Hess
4. Vytautas Iesmantavicius
5. Josip Ahel
6. Alex Charles Tuck
7. Fabio Mohn
8. Marc Bühler

Reviewed by Review Commons

The Omicron (B.1.1.529) SARS-CoV-2 variant of concern also affects companion animals

1. Lidia Sánchez-Morales
2. José M. Sánchez-Vizcaíno
3. Marta Pérez-Sancho
4. Lucas Domínguez
5. Sandra Barroso-Arévalo

Reviewed by ScreenIT

Disrupting ACE2 Dimerization Mitigates the Infection by SARS-COV-2

1. Jiaqi Zhu
2. Yue Su
3. Young Tang

Reviewed by ScreenIT

Biphasic regulation of osteoblast development via the ERK MAPK–mTOR pathway

1. Jung-Min Kim
2. Yeon-Suk Yang
3. Jaehyoung Hong
4. Sachin Chaugule
5. Hyonho Chun
6. Marjolein CH van der Meulen
7. Ren Xu
8. Matthew B Greenblatt
9. Jae-hyuck Shim

• Curated by eLife

  Evaluation Summary:

  This work provides a novel insight into regulation of osteogenesis by ERK-mTOR pathway. The authors proposed that the effect of Erk pathway would be mediated mTOR2-SGK1. The mitochondrial metabolisms appears to be involved in this regulation. This study is well performed, and the manuscript is clearly written.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation

1. Morgane Boone
2. Lan Wang
3. Rosalie E Lawrence
4. Adam Frost
5. Peter Walter
6. Michael Schoof

• Curated by eLife

  Evaluation Summary:

  This manuscript addresses a significant and timely topic in translational control and will be of interest to researchers studying molecular biology or diseases impacted by the Integrated Stress Response (ISR). The combination of biochemical, structural, and in-cell experiments constitutes a comprehensive study that supports the proposed model for allosteric regulation of the active/inactive states of the eIF2B complex. The findings are relevant to neuropathologies, infectious and inflammatory diseases, diabetes, and metabolic disorders.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation

1. Rafael Romero-Becerra
2. Alfonso Mora
3. Elisa Manieri
4. Ivana Nikolic
5. Ayelén Melina Santamans
6. Valle Montalvo-Romeral
7. Francisco Miguel Cruz
8. Elena Rodríguez
9. Marta León
10. Luis Leiva-Vega
11. Laura Sanz
12. Víctor Bondía
13. David Filgueiras-Rama
14. Luis Jesús Jiménez-Borreguero
15. José Jalife
16. Barbara Gonzalez-Teran
17. Guadalupe Sabio

• Curated by eLife

  Evaluation Summary:

  This paper demonstrates that deletion of MKK6 reduces life span in mice, and leads to cardiac hypertrophy that progresses to cardiac dilatation and fibrosis with age. The authors also demonstrate that the mechanism for this phenomenon is through reduced p38a activation while causing MKK3-p38g/d hyperphosphorylation and increased mTOR signaling. The authors extend previous studies (that demonstrate a role for P38 proteins as downstream effector of MKK6) and identify the isoform of P38 that plays a role in this process. Overall, the studies in this paper are conducted carefully and most of the conclusions are based on the reported data.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife