Molecular Biology

Integrative omics analysis reveals gene regulatory mechanisms distinguishing organoid-derived hepatocytes from primary human hepatocytes

1. Haoyu Wu
2. Annie S. P. Yang
3. Suzan Stelloo
4. Floris J. M. Roos
5. René H. M. te Morsche
6. Anne H. Verkerk
7. Maria V. Luna-Velez
8. Laura Wingens
9. Johannes H. W. de Wilt
10. Robert W. Sauerwein
11. Klaas W. Mulder
12. Simon J. van Heeringen
13. Monique M. A. Verstegen
14. Luc J. W. van der Laan
15. Hendrik Marks
16. Richárd Bártfai

Reviewed by Review Commons

SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction

1. Stephen E Flaherty
2. Olivier Bezy
3. Brianna LaCarubba Paulhus
4. LouJin Song
5. Mary Piper
6. Jincheng Pang
7. Yoson Park
8. Shoh Asano
9. Yu-Chin Lien
10. John D Griffin
11. Andrew Robertson
12. Alan Opsahl
13. Dinesh Hirenallur Shanthappa
14. Youngwook Ahn
15. Evanthia Pashos
16. Rebecca A Simmons
17. Morris J Birnbaum
18. Zhidan Wu

• Curated by eLife

  eLife assessment

  This study combines molecular genetics and target validation to discover genes involved in obesity and determine their role. It was unanimously agreed that the work is important in terms of significance as it has conceptual and practical implications beyond metabolism, including embryonic and placental development. The strength of evidence is convincing from the use of their forward genetic screen in mice.

Reviewed by eLife

Binding to nucleosome poises human SIRT6 for histone H3 deacetylation

1. Ekaterina Smirnova
2. Emmanuelle Bignon
3. Patrick Schultz
4. Gabor Papai
5. Adam Ben Shem

• Curated by eLife

  eLife assessment

  This manuscript provides a useful reconstruction of the structure of the sirtuin-class histone deacetylase Sirt6 bound to a nucleosome based on cryo-EM observations, and additional characterization of the flexibility of the histone tails in the complex based on molecular dynamics simulations. While similar structures have recently been published elsewhere, this solid study supports the conclusions of those papers and also includes new insights into the potential dynamics of Sirt6 bound to a nucleosome, insights that help explain its substrate specificity.

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 R. 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

Mitochondrial genomes of Pleistocene megafauna retrieved from recent sediment layers of two Siberian lakes

1. Peter Andreas Seeber
2. Laura Batke
3. Yury Dvornikov
4. Alexandra Schmidt
5. Yi Wang
6. Kathleen Stoof-Leichsenring
7. Katie Moon
8. Samuel H Vohr
9. Beth Shapiro
10. Laura S Epp

• Curated by eLife

  eLife assessment

  This work presents convincing evidence for the presence of wooly mammoth/rhinoceros ancient environmental DNA (aeDNA) far from the time likely to host living individuals: what is effectively a genetic version of a geological inclusion. These are important findings that will have ramifications for the interpretation and conclusions extracted from aeDNA more generally.

Reviewed by eLife

Mobile barrier mechanisms for Na+-coupled symport in an MFS sugar transporter

1. Parameswaran Hariharan
2. Yuqi Shi
3. Satoshi Katsube
4. Katleen Willibal
5. Nathan D Burrows
6. Patrick Mitchell
7. Amirhossein Bakhtiiari
8. Samantha Stanfield
9. Els Pardon
10. H Ronald Kaback
11. Ruibin Liang
12. Jan Steyaert
13. Rosa Viner
14. Lan Guan

• Curated by eLife

  eLife assessment

  In an important study that will be of interest to the mechanistic membrane transport community, the authors capture the first cryo-EM structure of the inward facing melbiose transporter MelB, a well-studied model transporter from the major facilitator (MFS) superfamily. Cryo-EM experiments and supporting biophysical experiments provide solid evidence for transporter conformational changes.

Reviewed by eLife

Cohesin still drives homologous recombination repair of DNA double-strand breaks in late mitosis

1. Jessel Ayra-Plasencia
2. Lorraine Symington
3. Félix Machín

• Curated by eLife

  eLife assessment

  This study presents evidence that suggests that the coalescence of sister chromatids induced by global double-strand DNA breaks (DSBs) during late mitosis is mediated by cohesin SMC3. These findings are valuable for studying the mechanism of eukaryotic cells to repair DNA during late mitosis. Although the discrete DSB induction system in budding yeast is sound, the strength of evidence is incomplete and could be buttressed to better support the major claims and to represent a clear advance with respect to the authors' previous contributions to this field.

Reviewed by eLife

Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis

1. Kyounghee Min
2. Batuhan Yenilmez
3. Mark Kelly
4. Dimas Echeverria
5. Michael Elleby
6. Lawrence M Lifshitz
7. Naideline Raymond
8. Emmanouela Tsagkaraki
9. Shauna M Harney
10. Chloe DiMarzio
11. Hui Wang
12. Nicholas McHugh
13. Brianna Bramato
14. Brett Morrison
15. Jeffery D Rothstein
16. Anastasia Khvorova
17. Michael P Czech

• Curated by eLife

  eLife assessment

  This convincing manuscript represents a valuable advance in understanding the role of MCT1 – a transporter for lactate and other organic anions – in hepatocytes and hepatic stellate cells in the liver. The authors also generate exciting new tools to investigate hepatic stellate cell biology, and these may have much broader applications, but future studies are required to validate these new tools.

Reviewed by eLife

Cryo-EM structure of cell-free synthesized human histamine H ₂ receptor coupled to heterotrimeric G _s protein in lipid nanodisc environment

1. Zoe Köck
2. Kilian Schnelle
3. Margherita Persechino
4. Simon Umbach
5. Hannes Schihada
6. Dovile Januliene
7. Kristian Parey
8. Steffen Pockes
9. Peter Kolb
10. Volker Dötsch
11. Arne Möller
12. Daniel Hilger
13. Frank Bernhard

Reviewed by PREreview

KIS counteracts PTBP2 and regulates alternative exon usage in neurons

1. Marcos Moreno-Aguilera
2. Alba M Neher
3. Mónica B Mendoza
4. Martin Dodel
5. Faraz K Mardakheh
6. Raúl Ortiz
7. Carme Gallego

Reviewed by Review Commons