Molecular Biology

Mechanisms governing target search and binding dynamics of hypoxia-inducible factors

1. Yu Chen
2. Claudia Cattoglio
3. Gina M Dailey
4. Qiulin Zhu
5. Robert Tjian
6. Xavier Darzacq

• Curated by eLife

  Evaluation Summary:

  The notion of transcription factors as composed of interchangeable parts where DNA binding activity can be separated from activation activity has been a dominant paradigm in molecular biology for decades. However, recent evidence suggests that activation domains may contribute to binding specificity as well. This paper describes the use of single-molecule imaging of endogenously tagged transcription factors to dissect how transcription factors move in the nucleus and how these dynamics are related to functional protein domains. These results will be of interest to the transcription and gene regulation fields, but the conclusions require additional experimental support.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Post‐transcriptional polyadenylation site cleavage maintains 3′‐end processing upon DNA damage

1. Rym Sfaxi
2. Biswendu Biswas
3. Galina Boldina
4. Mandy Cadix
5. Nicolas Servant
6. Huimin Chen
7. Daniel R Larson
8. Martin Dutertre
9. Caroline Robert
10. Stéphan Vagner

Reviewed by Review Commons

Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila

1. Joyce Rigal
2. Ane Martin Anduaga
3. Elena Bitman
4. Emma Rivellese
5. Sebastian Kadener
6. Michael T Marr

• Curated by eLife

  Evaluation Summary:

  This manuscript examines the role of transposable element (TE) expression and the transcription factor FOXO on aging of Drosophila melanogaster. Increased TE expression in aged organisms compared to their younger counterparts has been observed in several animals, including Drosophila. Here, the authors show that artificially inducing transcription of a specific TE can reduce fly lifespan and exacerbate some aging phenotypes-paraquat resistance and rhythmicity. The authors also argue that the detrimental effects of increased TE expression can be rescued by FOXO expression, although this is less convincing.

  (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

Alternative splicing of apoptosis genes promotes human T cell survival

1. Davia Blake
2. Caleb M Radens
3. Max B Ferretti
4. Matthew R Gazzara
5. Kristen W Lynch

• Curated by eLife

  Evaluation Summary:

  Apoptotic regulators have long been known to often be expressed in pairs of pro- and anti-apoptotic isoforms. This demonstration of how a program of these splicing changes contributes to immune responses adds an important new understanding of both apoptosis and T cell 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

A parasitic fungus employs mutated eIF4A to survive on rocaglate-synthesizing Aglaia plants

1. Mingming Chen
2. Naoyoshi Kumakura
3. Hironori Saito
4. Ryan Muller
5. Madoka Nishimoto
6. Mari Mito
7. Pamela Gan
8. Nicholas T Ingolia
9. Ken Shirasu
10. Takuhiro Ito
11. Yuichi Shichino
12. Shintaro Iwasaki

• Curated by eLife

  Evaluation Summary:

  In this important paper, Chen and colleagues identify a species of fungus, Ophiocordyceps sp. BRM1, that is able to grow on Aglaia sp. plants despite their production of rocaglate inhibitors of the eIF4A translation initiation factor. Through a series of solid experiments, the authors identify an amino acid substitution encoded in the fungal eIF4A gene that preserves eIF4A activity in the presence of these compounds. The authors conclude the substitution evolved to bypass this defense mechanism, similar to the way in which the plant itself bypasses it. The work will be of interest to fungal biologists and colleagues studying plant-microbe interactions.

  (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

A novel SATB1 protein isoform with different biophysical properties

1. Tomas Zelenka
2. Dionysios-Alexandros Papamatheakis
3. Petros Tzerpos
4. Giorgos Panagopoulos
5. Konstantinos C. Tsolis
6. Vassilis M. Papadakis
7. Dimitris Mariatos Metaxas
8. George Papadogkonas
9. Eleftherios Mores
10. Manouela Kapsetaki
11. Joseph Papamatheakis
12. David Stanek
13. Charalampos Spilianakis

Reviewed by Review Commons

Highly efficient generation of isogenic pluripotent stem cell models using prime editing

1. Hanqin Li
2. Oriol Busquets
3. Yogendra Verma
4. Khaja Mohieddin Syed
5. Nitzan Kutnowski
6. Gabriella R Pangilinan
7. Luke A Gilbert
8. Helen S Bateup
9. Donald C Rio
10. Dirk Hockemeyer
11. Frank Soldner

• Curated by eLife

  Evaluation Summary:

  In this manuscript, Li et al directly compare different editing strategies for human pluripotent stem cells. They demonstrate that prime editing is more efficient and precise, compared with double-strand break-based methods. They also confirm the suitability of prime editing for the introduction of different mutations related to Parkinson's disease as a model.

  (This preprint has been reviewed by eLife. We include the joint public review 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

RNA localization mechanisms transcend cell morphology

1. Raeann Goering
2. Ankita Arora
3. Megan C Pockalny
4. J Matthew Taliaferro

• Curated by eLife

  Evaluation Summary:

  Goering and colleagues investigate subcellular RNA localization across different cell types and species. The major insight is that there may be general mechanisms and specifically conserved proteins that regulate RNA localization in diverse cell types and morphologies. This manuscript will be of interest to those studying gene expression and how its regulation occurs within the cell.

  (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

Validation of scRNA-seq by scRT-ddPCR using the example of ErbB2 in MCF7 cells

1. Tobias Lange
2. Tobias Groß
3. Ábris Jeney
4. Julia Scherzinger
5. Elly Sinkala
6. Christoph Niemöller
7. Stefan Zimmermann
8. Peter Koltay
9. Felix von Stetten
10. Roland Zengerle
11. Csaba Jeney

Reviewed by Review Commons

Disruption of Smarce1, a component of the SWI/SNF chromatin remodeling complex, decreases nucleosome stability in mouse embryonic stem cells and impairs differentiation

1. Katsunobu Kashiwagi
2. Junko Yoshida
3. Hiroshi Kimura
4. Kyoji Horie

Reviewed by Review Commons