Molecular Biology

Molecular mechanism of Afadin substrate recruitment to the receptor phosphatase PTPRK via its pseudophosphatase domain

1. Iain M Hay
2. Katie E Mulholland
3. Tiffany Lai
4. Stephen C Graham
5. Hayley J Sharpe
6. Janet E Deane

• Curated by eLife

  Evaluation Summary:

  These studies establish a role for the D2 pseudophosphatase domain of the PTPRK receptor-like phosphotyrosine phosphatase in recruiting Afadin, a cell-cell junction protein that is reported to be a PTPRK substrate, for dephosphorylation by the active D1 phosphatase domain. These findings suggest that the D2 pseudophosphatase domains of RPTPKs might have a general function as platforms to recruit specific phosphotyrosine substrates.

  (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

Development of a versatile high-throughput mutagenesis assay with multiplexed short-read NGS using DNA-barcoded supF shuttle vector library amplified in E. coli

1. Hidehiko Kawai
2. Ren Iwata
3. Shungo Ebi
4. Ryusei Sugihara
5. Shogo Masuda
6. Chiho Fujiwara
7. Shingo Kimura
8. Hiroyuki Kamiya

Reviewed by Review Commons

Inhibited KdpFABC transitions into an E1 off-cycle state

1. Jakob M Silberberg
2. Charlott Stock
3. Lisa Hielkema
4. Robin A Corey
5. Jan Rheinberger
6. Dorith Wunnicke
7. Victor RA Dubach
8. Phillip J Stansfeld
9. Inga Hänelt
10. Cristina Paulino

• Curated by eLife

  Evaluation Summary:

  KdpFABC is a bacterial potassium uptake transporter made up of a channel-like subunit (KdpA) and a P-type ATPase (KdpB). When potassium levels are low (< 2 mM), the transporter actively and selectively uptakes potassium, but must be switched off again to prevent excessive K+ accumulation. Although structures of KdpFABC have been determined before, the structural basis for inhibition by phosphorylation is unknown. Here, the authors have determined the structure of KdpABC in an arrested (off-state) that is in a distinct conformation from previously determined P-type ATPase structures. More detailed structural comparisons are needed to more convincingly show this, however, and the protein required to inhibit KdpABC by phosphorylation remains unknown. This paper will be of interest to researchers in the microbiology and transporter communities.

  (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

An atrial fibrillation-associated regulatory region modulates cardiac Tbx5 levels and arrhythmia susceptibility

1. Fernanda M Bosada
2. Karel van Duijvenboden
3. Alexandra E Giovou
4. Mathilde R Rivaud
5. Jae-Sun Uhm
6. Arie O Verkerk
7. Bastiaan J Boukens
8. Vincent M Christoffels

• Curated by eLife

  Evaluation Summary:

  This manuscript presents an interesting and informative study on two regulatory elements found near atrial fibrillation-associated regions and their effect on Tbx5 expression and arrhythmia susceptibility in a mouse model. The multilevel approaches and analyses are rigorous, and the conclusions are justified by the data. Tbx5 expression may be of relevance for human atrial fibrillation and disease risk in patients, and the work is of potential interest to scientists in the fields of gene dosage, gene regulation, genetic susceptibility, genetic variants and cardiovascular 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

Structure of a bacterial ribonucleoprotein complex central to the control of cell envelope biogenesis

1. Md Saiful Islam
2. Steven W Hardwick
3. Laura Quell
4. Svetlana Durica‐Mitic
5. Dimitri Y Chirgadze
6. Boris Görke
7. Ben F Luisi

Reviewed by Review Commons

SRSF6 balances mitochondrial-driven innate immune outcomes through alternative splicing of BAX

1. Allison R Wagner
2. Chi G Weindel
3. Kelsi O West
4. Haley M Scott
5. Robert O Watson
6. Kristin L Patrick

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to people studying how differentially spliced genes regulate biological processes, and in particular, those interested in the intersection of cell death and immunity. This work offers new insight into how an alternatively spliced protein with a well-known function in cell death regulates the basal expression of genes involved in immunity and sensitizes cells to apoptotic cell death. Overall, the major conclusions are supported by the data but more investigation is needed to support the mechanism by which BAX splicing is inducing the phenotypes observed.

  (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

Invigorating human MSCs for transplantation therapy via Nrf2/DKK1 co-stimulation in a mice acute-on-chronic liver failure model

1. Feng Chen
2. Zhaodi Che
3. Yingxia Liu
4. Pingping Luo
5. Lu Xiao
6. Yali Song
7. Cunchuan Wang
8. Zhiyong Dong
9. Mianhuan Li
10. George L. Tipoe
11. Dongqing Wu
12. Min Yang
13. Yi Lv
14. Fei Wang
15. Hua Wang
16. Jia Xiao

• Curated by eLife

  Evaluation Summary:

  Chen et al. demonstrate a pro-survival role of the NRF2/DKK1 axis in mesenchymal stem cells. Furthermore, the authors provide evidence that targeting this pathway can enhance survival in response to liver failure in vivo. These data highlight a novel signaling pathway to enhance efficacy of MSCs in promoting regeneration.

  (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

RNA sequence to structure analysis from comprehensive pairwise mutagenesis of multiple self-cleaving ribozymes

1. Jessica M Roberts
2. James D Beck
3. Tanner B Pollock
4. Devin P Bendixsen
5. Eric J Hayden

• Curated by eLife

  Evaluation Summary:

  The authors provide a summary of single and double mutants in five self-cleaving ribozymes using next-generation sequencing. They dissect their data in terms of epistasis effects, which provides a new angle to understanding ribozyme function. In principle, this allows conclusions to be drawn on bases involved in pairs and in catalysis that have the potential to be of use to the field, although there is also a series of technical weaknesses that should be addressed.

  (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

The SPARC complex defines RNAPII promoters in Trypanosoma brucei

1. Desislava P Staneva
2. Stefan Bresson
3. Tatsiana Auchynnikava
4. Christos Spanos
5. Juri Rappsilber
6. A Arockia Jeyaprakash
7. David Tollervey
8. Keith R Matthews
9. Robin C Allshire

Reviewed by Review Commons

FACT regulates pluripotency through proximal and distal regulation of gene expression in murine embryonic stem cells

1. David C. Klein
2. Santana M. Lardo
3. Kurtis N. McCannell
4. Sarah J. Hainer

Reviewed by Review Commons