Genetics

Structural and functional conservation of the programmed −1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2)

1. Jamie A. Kelly
2. Alexandra N. Olson
3. Krishna Neupane
4. Sneha Munshi
5. Josue San Emeterio
6. Lois Pollack
7. Michael T. Woodside
8. Jonathan D. Dinman

Reviewed by ScreenIT

Perturb-tracing enables high-content screening of multiscale 3D genome regulators

1. Yubao Cheng
2. Mengwei Hu
3. Bing Yang
4. Tyler B Jensen
5. Tianqi Yang
6. Ruihuan Yu
7. Zhaoxia Ma
8. Jonathan S D Radda
9. Shengyan Jin
10. Chongzhi Zang
11. Siyuan Wang

Reviewed by Arcadia Science

The genomic footprint of social stratification in admixing American populations

1. Alex Mas-Sandoval
2. Sara Mathieson
3. Matteo Fumagalli

• Curated by eLife

  eLife assessment

  This valuable study combines population genetic theory and deep learning approaches to estimate the extent of assortative mating and sex bias in modern admixed populations in the Americas. The new approach provides solid evidence for their main conclusions that socially constructed hierarchies have influenced mating behaviors, though certain results would benefit from further consideration. This paper would be of interest to human population geneticists and social scientists, particularly those studying demographic processes.

Reviewed by eLife

Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues

1. Ambre J. Sala
2. Rogan A. Grant
3. Ghania Imran
4. Claire Morton
5. Renee M. Brielmann
6. Laura C. Bott
7. Jennifer Watts
8. Richard I. Morimoto

Reviewed by Arcadia Science

Homeodomain-interacting protein kinase maintains neuronal homeostasis during normal Caenorhabditis elegans aging and systemically regulates longevity from serotonergic and GABAergic neurons

1. Maria I Lazaro-Pena
2. Adam B Cornwell
3. Carlos A Diaz-Balzac
4. Ritika Das
5. Zachary C Ward
6. Nicholas Macoretta
7. Juilee Thakar
8. Andrew V Samuelson

• Curated by eLife

  eLife assessment

  This fundamental study substantially advances our understanding of how aging and stress resilience across an organism is determined by identifying a new player in this process and uncovering its mode of action. The evidence is solid as the methods, data and analyses broadly support the claims with only minor weaknesses. The work will be of broad interest to the field of aging and protein homeostasis.

Reviewed by eLife

Engineering of the endogenous HBD promoter increases HbA2

1. Mandy Y Boontanrart
2. Elia Mächler
3. Simone Ponta
4. Jan C Nelis
5. Viviana G Preiano
6. Jacob E Corn

• Curated by eLife

  eLife assessment

  This study presents the important finding that gene editing could be used to activate delta-globin expression to treat disorders of red blood cell synthesis. The evidence supporting the claims of the authors is solid, particularly in the immortalized cell lines, although inclusion of a larger number of donor patient samples may have strengthened the conclusions that were able to be drawn from the primary cell experiments. The data show this approach to have promise and identify avenues of effort that could be pursued to advance it to a clinical strategy for hemoglobinopathy treatment.

Reviewed by eLife

Mec1-independent activation of the Rad53 checkpoint kinase revealed by quantitative analysis of protein localization dynamics

1. Brandon Ho
2. Ethan J Sanford
3. Raphael Loll-Krippleber
4. Nikko P Torres
5. Marcus B Smolka
6. Grant W Brown

• Curated by eLife

  eLife Assessment:

  In addition to identifying several components regulated by checkpoint kinases, the authors identify a novel non-canonical activation mode for the central checkpoint kinase Rad53, a phosphorylation event that does not depend on Mec1 and instead depends on proteins involved in retrograde signaling through Rtg3. The study thus reveals unanticipated complexities in the DNA replication stress response. Overall, the work is well done and the data support the main conclusions.

Reviewed by eLife

A critical region of A20 unveiled by missense TNFAIP3 variations that lead to autoinflammation

1. Elma El Khouri
2. Farah Diab
3. Camille Louvrier
4. Eman Assrawi
5. Aphrodite Daskalopoulou
6. Alexandre Nguyen
7. William Piterboth
8. Samuel Deshayes
9. Alexandra Desdoits
10. Bruno Copin
11. Florence Dastot Le Moal
12. Sonia Athina Karabina
13. Serge Amselem
14. Achille Aouba
15. Irina Giurgea

• Curated by eLife

  eLife assessment

  This manuscript is of big interest to physicians and geneticists who may struggle with interpreting the clinical significance of novel or rare missense variants in the TNFAIP3 gene in patients with systemic inflammatory diseases. There is also much debate about the potential mechanisms by which these missense mutations might be pathogenic. El Khour et al. addressed these questions by using a combination of in silico analysis and in vitro functional assays. However, their conclusions require additional experimental support and should be expanded to include other reported likely pathogenic missense variants.

Reviewed by eLife

Environment- and epigenome-wide association study of obesity in ‘Children of 1997’ birth cohort

1. Jie Zhao
2. Bohan Fan
3. Jian Huang
4. Benjamin John Cowling
5. Shiu Lun Ryan Au Yeung
6. Andrea Baccarelli
7. Gabriel M Leung
8. C Mary Schooling

• Curated by eLife

  eLife assessment

  This study presents useful information on the environmental and epigenomic associations of obesity in children and adolescents. The data were collected and analyzed using a solid and validated methodology and can be referenced at the clinics and health authorities to make a guideline and a policy strategy.

Reviewed by eLife

Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates

1. Adele Francis Xu
2. Rut Molinuevo
3. Elisa Fazzari
4. Harrison Tom
5. Zijian Zhang
6. Julien Menendez
7. Kerriann M Casey
8. Davide Ruggero
9. Lindsay Hinck
10. Jonathan K Pritchard
11. Maria Barna

• Curated by eLife

  eLife assessment

  This study reports a cutting-edge set of experiments examining evolutionary models of paralog function differentiation for the mammalian ribosomal proteins eS27 and eS27L. No differentiated roles were identified for either paralog, but the paralogs are differentially expressed, and they preferentially associate with different transcript classes. Reciprocal switching of their coding sequences yielded no detectable phenotypes, but loss of either paralog resulted in lethality at different developmental stages, suggesting that subfunctionalized expression patterns underlie the retention of these paralogs. The work will be of interest to colleagues studying the evolution and diversification of ribosomes.

Reviewed by eLife