Genetics

Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants

1. Helena Hinterding
2. Maarouf Baghdadi
3. Thies Gehrmann
4. Pasquale Putter
5. Mara Neuerburg
6. Nico Lakenberg
7. Erik B. van den Akker
8. P. Eline Slagboom
9. Joris Deelen
10. Linda Partridge

Reviewed by Review Commons

Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging

1. Laxmi Rathor
2. Shayla Curry
3. Youngyong Park
4. Taylor McElroy
5. Briana Robles
6. Yi Sheng
7. Wei-Wen Chen
8. Kisuk Min
9. Rui Xiao
10. Myon Hee Lee
11. Sung Min Han

• Curated by eLife

  eLife assessment

  This study interrogates cell non-autonomous signaling between GABAergic neurons and somatic tissues in the nematode C. elegans. The authors report that mitochondrial stress in only GABAergic neurons extends lifespan and improves healthspan, phenotypes that are dependent on the transcription factor daf-16/FOXO3a. However, while the findings may be valuable to furthering our understanding of neuronal control of aging and health, the current evidence is incomplete and additional experiments are needed to support their claims.

Reviewed by eLife

Functional dissection of complex and molecular trait variants at single nucleotide resolution

1. Layla Siraj
2. Rodrigo I Castro
3. Hannah Dewey
4. Susan Kales
5. Thanh Thanh L Nguyen
6. Masahiro Kanai
7. Daniel Berenzy
8. Kousuke Mouri
9. Qingbo Wang
10. Zachary R McCaw
11. Sager J Gosai
12. François Aguet
13. Ran Cui
14. Christopher M Vockley
15. Caleb A Lareau
16. Yukinori Okada
17. Alexander Gusev
18. Thouis R Jones
19. Eric S Lander
20. Pardis C Sabeti
21. Hilary K Finucane
22. Steven K Reilly
23. Jacob C Ulirsch
24. Ryan Tewhey

Reviewed by Arcadia Science

The RNA-binding activity of the TRIM-NHL protein NHL-2 is essential for miRNA-mediated gene regulation

1. Nasim Saadat
2. Rhys N. Colson
3. Acadia L. Grimme
4. Uri Seroussi
5. Joshua W. Anderson
6. Julie M. Claycomb
7. Matthew C. J. Wilce
8. Katherine McJunkin
9. Jacqueline A. Wilce
10. Peter R. Boag

• Curated by eLife

  eLife assessment

  This useful study identifies amino acid residues in the C. elegans RNA-binding protein NHL-2 that are required for RNA binding in vitro and NHL-2 function in vivo. The evidence in support of the authors' mechanistic model is currently incomplete, as data implicating specific NHL-2 amino acids in RNA binding per se in vivo are not presented. This manuscript will be of interest to scientists working in the area of gene regulation.

Reviewed by eLife

Biobank-wide association scan identifies risk factors for late-onset Alzheimer’s disease and endophenotypes

1. Donghui Yan
2. Bowen Hu
3. Burcu F Darst
4. Shubhabrata Mukherjee
5. Brian W Kunkle
6. Yuetiva Deming
7. Logan Dumitrescu
8. Yunling Wang
9. Adam Naj
10. Amanda Kuzma
11. Yi Zhao
12. Hyunseung Kang
13. Sterling C Johnson
14. Cruchaga Carlos
15. Timothy J Hohman
16. Paul K Crane
17. Corinne D Engelman
18. Alzheimer’s Disease Genetics Consortium (ADGC)
19. Qiongshi Lu

• Curated by eLife

  eLife assessment

  In the last 15 years, large-scale association studies (GWAS) have served to estimate the association between genome-wide common variants and a large number of disparate traits and diseases in humans. This valuable method provides a new way to find correlations between the genetic component of a phenotype of interest, and all this wealth of genetic information. This software adds as a new tool to investigate genetic correlation between traits, and to generate new mechanistic hypotheses and dissect the role of the observed associations in disease heterogeneity. The results of the application of their method are solid and generally agree with what others have seen using similar AD and UKB data.

Reviewed by eLife

Natural variation in infection specificity of Caenorhabditis briggsae isolates by two RNA viruses

1. Cigdem Alkan
2. Gautier Brésard
3. Lise Frézal
4. Aurélien Richaud
5. Albane Ruaud
6. Gaotian Zhang
7. Marie-Anne Félix

Reviewed by Review Commons

Mono-methylated histones control PARP-1 in chromatin and transcription

1. Gbolahan Bamgbose
2. Guillaume Bordet
3. Niraj Lodhi
4. Alexei Tulin

• Curated by eLife

  eLife assessment

  This valuable study presents convincing evidence for an association between PARP-1 and H4K20me1 in transcriptional regulation, supported by biochemical and ChIP-seq analyses. The work contributes significantly to our understanding of how Parp1 associates with target genes to regulate their expression.

Reviewed by eLife

Lack of evidence supporting transgenerational effects of non-transmitted paternal alleles on the murine transcriptome

1. Rodrigo Gularte-Mérida
2. Carole Charlier
3. Michel Georges

• Curated by eLife

  eLife assessment

  This important article presents the results of a large screen for non-genetic transgenerational effects that may influence gene expression and other phenotypes in mice. An extraordinary amount of mouse breeding, phenotyping, and RNA sequencing data provide compelling evidence that, for the phenotypes and genomic regions interrogated in these mouse strains, non-genetic transgenerational effects of appreciable magnitude are likely to be extremely rare. This paper will be of broad interest to geneticists and of particular interest to those studying epigenetic inheritance.

Reviewed by eLife

Exploring functional conservation in silico : a new machine learning approach to RNA-editing

1. Michał Zawisza-Álvarez
2. Jesús Peñuela-Melero
3. Esteban Vegas
4. Ferran Reverter
5. Jordi Garcia-Fernàndez
6. Carlos Herrera-Úbeda

Reviewed by Review Commons

Imputation of 3D genome structure by genetic–epigenetic interaction modeling in mice

1. Lauren Kuffler
2. Daniel A Skelly
3. Anne Czechanski
4. Haley J Fortin
5. Steven C Munger
6. Christopher L Baker
7. Laura G Reinholdt
8. Gregory W Carter

• Curated by eLife

  eLife assessment

  This important manuscript reports interactions between genetic variation, DNA accessibility, and chromatin structure in gene expression at a genome wide scale. The authors found that most of these interactions occur within topologically associating domains (TADs) and 3D genome structure data can be efficiently used to guide the discovery of significant genetic and epigenetic influences on gene expression. Overall, this convincing study highlights the importance of 3D chromatin structure in controlling how gene expression is regulated by genetic and epigenetic processes.

Reviewed by eLife