Molecular Biology

Affinity-tagged SMAD1 and SMAD5 mouse lines reveal transcriptional reprogramming mechanisms during early pregnancy

1. Zian Liao
2. Suni Tang
3. Kaori Nozawa
4. Keisuke Shimada
5. Masahito Ikawa
6. Diana Monsivais
7. Martin Matzuk

• Curated by eLife

  eLife assessment

  This study presents two valuable new mouse models that individually tag proteins from the SMAD family to identify distinct roles during early pregnancy. Convincing evidence is provided that SMAD1 and SMAD5 target many of the same genomic regions as each other and the progesterone receptor. Given the broad effect of these signaling pathways in multiple systems, these new tools will most likely interest readers across biological disciplines.

Reviewed by eLife

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

1. Kejia Zhang
2. Patrick Eldin
3. Jessica H Ciesla
4. Laurence Briant
5. Jenna M Lentini
6. Jillian Ramos
7. Justin Cobb
8. Joshua Munger
9. Dragony Fu

• Curated by eLife

  eLife assessment

  This manuscript provides important insights into the degradation of the host tRNA modification enzyme TRMT1 by the SARS-CoV-2 protease Nsp5 (nonstructural protein 5 or MPro). The data convincingly support the main conclusions of the paper. These results will be of interest to virologists studying the alterations in tRNA modifications, host methyltransferases, and viral infections.

Reviewed by eLife

Synthetic type III-E CRISPR-Cas effectors for programmable RNA-targeting

1. Daniel J. Brogan
2. Elena Dalla Benetta
3. Tianqi Wang
4. Calvin P. Lin
5. Fangying Chen
6. Harry Li
7. Claire Lin
8. Elizabeth A. Komives
9. Omar S. Akbari

Reviewed by Arcadia Science

Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation

1. Wayne Mitchell
2. Ludger JE Goeminne
3. Alexander Tyshkovskiy
4. Sirui Zhang
5. Julie Y Chen
6. Joao A Paulo
7. Kerry A Pierce
8. Angelina H Choy
9. Clary B Clish
10. Steven P Gygi
11. Vadim N Gladyshev

• Curated by eLife

  eLife assessment

  This important study reports comprehensive multi-omics data on the changes induced in young and aged male mouse tail fibroblasts after treatment with chemical reprogramming factors. The authors provide solid evidence to support their claim that chemical reprogramming factors induce changes consistent with a reduction of cellular 'biological' age (e.g., correlations with established aging markers in whole tissues).

Reviewed by eLife

A myristoyl switch at the plasma membrane triggers cleavage and oligomerization of Mason-Pfizer monkey virus matrix protein

1. Markéta Častorálová
2. Jakub Sýs
3. Jan Prchal
4. Anna Pavlů
5. Lucie Prokopová
6. Zina Briki
7. Martin Hubálek
8. Tomas Ruml

• Curated by eLife

  eLife assessment

  This valuable study advances our understanding of how the viral protease in a D-type retrovirus is activated and in particular how the exposure of the myristoyl group is required for processing of the Gag matrix precursor. The supporting evidence is convincing, but the work would benefit from additional data in support of the claims. This manuscript is of interest to retrovirologists and structural biologists.

Reviewed by eLife

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

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