Molecular Biology

Time-resolved mitochondrial-focused screening identifies regulatory components of oxidative metabolism

1. Marcos Zamora-Dorta
2. Sara Laine-Menéndez
3. David Abia
4. Pilar González-García
5. Luis C. López
6. Paula Fernández-Montes Díaz
7. Enrique Calvo
8. Jesús Vázquez
9. José Antonio Enríquez
10. Eduardo Balsa

Reviewed by Arcadia Science

Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain

1. Gabriella O Estevam
2. Edmond M Linossi
3. Christian B Macdonald
4. Carla A Espinoza
5. Jennifer M Michaud
6. Willow Coyote-Maestas
7. Eric A Collisson
8. Natalia Jura
9. James S Fraser

• Curated by eLife

  eLife assessment

  This manuscript describes a deep mutational scanning study of the kinase domain of the MET receptor tyrosine kinase. The study yields an important catalog of essentially all possible deleterious mutations in this portion of the receptor., with convincing evidence. The manuscript will be of interest to researchers working in the field of receptor tyrosine kinases.

Reviewed by eLife

Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides

1. Meng-Hsuan Hsiao
2. Yang Miao
3. Zixing Liu
4. Konstantin Schütze
5. Nathachit Limjunyawong
6. Daphne Chun-Che Chien
7. Wayne Denis Monteiro
8. Lee-Shin Chu
9. William Morgenlander
10. Sahana Jayaraman
11. Sung-eun Jang
12. Jeffrey J. Gray
13. Heng Zhu
14. Xinzhong Dong
15. Martin Steinegger
16. H. Benjamin Larman

Reviewed by Arcadia Science

Ais: streamlining segmentation of cryo-electron tomography datasets

1. Mart G.F. Last
2. Leoni Abendstein
3. Lenard M. Voortman
4. Thomas H. Sharp

• Curated by eLife

  eLife assessment

  This work describes a new software platform for machine-learning-based segmentation of and particle-picking in cryo-electron tomograms. The program and its corresponding online database of trained models will allow experimentalists to conveniently test different models and share their results with others. The paper provides solid evidence that the software will be valuable to the community.

Reviewed by eLife

Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9

1. Joshua D Eaton
2. Jessica Board
3. Lee Davidson
4. Chris Estell
5. Steven West

• Curated by eLife

  eLife assessment

  The important study uses a new experimental method to provide compelling evidence on how sense- and anti-sense transcription is differentially regulated. The method described here can generally be used to study the alterations in transcription. This paper will be of interest to scientists working in the gene regulation community.

Reviewed by eLife

Human immunodeficiency virus-1 induces host genomic R-loop and preferentially integrates its genome near the R-loop regions

1. Kiwon Park
2. Dohoon Lee
3. Jiseok Jeong
4. Sungwon Lee
5. Sun Kim
6. Kwangseog Ahn

• Curated by eLife

  eLife assessment

  Based on largely indirect evidence, this study proposes that genomic integration of HIV targets DNA/RNA hybrids called R-loops. The evidence is indirect because the authors do not use relevant models systems to show integration and because they artificially induce R-loops in the critical experiments. There are two interrelated findings: 1) VSVg-pseudotyped HIV-1 induces R-loops in various cell types, and 2) VSVg-pseudotyped HIV-1 targets R-loops for integration in an artificial Hela cell model in which R-loops are exogenously induced. The induction of R-loops by a pseudotyped HIV-1 is a potentially valuable finding. Critically, however, because of the caveats above, the evidence is inadequate to support the primary claims in the title, abstract, and manuscript. Furthermore, if these claims were true, the authors do not provide context for how they could be reconciled with well-established structural data showing that HIV-1 integrase catalyzes the integration of viral DNA into dsDNA as a substrate.

Reviewed by eLife

Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity

1. Christin Krause
2. Jan H Britsemmer
3. Miriam Bernecker
4. Anna Molenaar
5. Natalie Taege
6. Nuria Lopez-Alcantara
7. Cathleen Geißler
8. Meike Kaehler
9. Katharina Iben
10. Anna Judycka
11. Jonas Wagner
12. Stefan Wolter
13. Oliver Mann
14. Paul Pfluger
15. Ingolf Cascorbi
16. Hendrik Lehnert
17. Kerstin Stemmer
18. Sonja C Schriever
19. Henriette Kirchner

• Curated by eLife

  eLife assessment

  Building on on the observation of an increase in miR-182-5p in diabetic patients, the authors investigated the role of miR-182-5p and its target gene LRP6 in dysregulated glucose tolerance and fatty acid metabolism in obese type 2 diabetics. The use of human livers complemented by supporting data in mice and cells are strengths, but the evidence presented remains incomplete. The findings provide valuable insights into the role of miRNAs in the regulation of liver metabolism and insulin sensitivity in individuals with diabetes and fatty liver disease.

Reviewed by eLife

The specific AMPK activator A-769662 ameliorates pathological phenotypes following mitochondrial DNA depletion

1. Gustavo Carvalho
2. Bruno Repolês
3. Tran V.H. Nguyen
4. Josefin M.E. Forslund
5. Farahnaz Ranjbarian
6. Isabela C. Mendes
7. Micol Falabella
8. Mara Doimo
9. Sjoerd Wanrooij
10. Robert D.S. Pitceathly
11. Anders Hofer
12. Paulina H. Wanrooij

Reviewed by Review Commons

Punctuated and continuous structural diversity of S-layers across the prokaryotic tree of life

1. Edward Johnston
2. Buse Isbilir
3. Vikram Alva
4. Tanmay A.M. Bharat
5. Jonathan P. K. Doye

Reviewed by Arcadia Science

Srs2 binding to PCNA and its sumoylation contribute to RPA antagonism during the DNA damage response

1. Jiayi Fan
2. Nalini Dhingra
3. Tammy Yang
4. Vicki Yang
5. Xiaolan Zhao

• Curated by eLife

  eLife assessment

  This manuscript reports valuable findings on the role of the Srs2 protein in turning off the DNA damage signaling response initiated by Mec1 (human ATR) kinase. The data provide solid evidence that Srs2 interaction with PCNA and ensuing SUMO modification is required for checkpoint downregulation. However, experimental evidence with regard to the model that Srs2 acts at gaps after camptothecin-induced DNA damage is currently lacking. The work will be of interest to cell biologists studying genome integrity but would be strengthened by considering the possible role of Rad51 and its removal.

Reviewed by eLife