Genetics

Impact of liver specific survival motor neuron (SMN) depletion on peripheral and central nervous system tissue pathology

1. Monique Marylin Alves de Almeida
2. Yves De Repentigny
3. Sabrina Gagnon
4. Emma R Sutton
5. Rashmi Kothary

• Curated by eLife

  eLife assessment

  This work presents a valuable mouse model for a liver-specific depletion of the Survival Motor Neuron (SMN) protein, where the liver retains 30% of functional full-length SMN protein. The authors provide a profile of phenotypic changes in liver-specific SMN depleted mice: while evidence supporting their claims are generally solid, the phenotype is mild and mechanistic understanding remains to be determined.

Reviewed by eLife

Transcription factor condensates, 3D clustering, and gene expression enhancement of the MET regulon

1. James Lee
2. Leman Simpson
3. Yi Li
4. Samuel Becker
5. Fan Zou
6. Xin Zhang
7. Lu Bai

• Curated by eLife

  eLife assessment

  This important study investigates the relationship between transcription factor condensate formation, transcription, and 3D gene clustering of the MET regulon in the model organism S. cerevisiae. The authors provide solid experimental evidence that transcription factor condensates enhance transcription of MET-regulated genes, but evidence for the role of Met4 IDRs and Met4-containing condensates in mediating target gene clustering in the MET regulon is not as strong. This paper will be of interest to molecular biologists working on chromatin and transcription, although its impact would be strengthened by further investigation.

Reviewed by eLife

Intergenerational transport of double-stranded RNA limits heritable epigenetic changes

1. Nathan Shugarts
2. Aishwarya Sathya
3. Andrew L Yi
4. Winnie M Chan
5. Julia A Marré
6. Antony M Jose

• Curated by eLife

  eLife assessment

  In this report, the authors present valuable findings identifying a novel worm-specific protein (sdg-1) that is induced upon loss of dsRNA import via SID-1, but is not required to mediate SID-1 RNA regulatory effects. The genetic and genomic approaches are well-executed. The existing data are solid, but the study would benefit from additional supporting evidence. The manuscript's central findings could also be refined to avoid overstating the results. These findings will be of interest to those working in the germline epigenetic inheritance field.

Reviewed by eLife

Tbx1 haploinsufficiency causes brain metabolic and behavioral anomalies in adult mice which are corrected by vitamin B12 treatment

1. Marianna Caterino
2. Debora Paris
3. Giulia Torromino
4. Michele Costanzo
5. Gemma Flore
6. Annabella Tramice
7. Elisabetta Golini
8. Silvia Mandillo
9. Diletta Cavezza
10. Claudia Angelini
11. Margherita Ruoppolo
12. Andrea Motta
13. Elvira De Leonibus
14. Antonio Baldini
15. Elizabeth Illingworth
16. Gabriella Lania

Reviewed by Review Commons

A CRISPR-Cas9-based system for the dose-dependent study of DNA double-strand breaks sensing and repair

1. Jocelyn Coiffard
2. Sylvain Kumanski
3. Olivier Santt
4. Benjamin Pardo
5. María Moriel-Carretero

Reviewed by Review Commons

Resetting of H3K4me2 during mammalian parental-to-zygote transition

1. Chong Wang
2. Yong Shi
3. Jia Guo
4. Kaiyue Hu
5. Yaqian Wang
6. Yang Li
7. Jiawei Xu

• Curated by eLife

  eLife assessment

  This study presents an important finding of dynamic reprogramming of global H3K4me2 during mouse oocyte-to-embryo transition. While the H3K4me2 epigenome data is convincing, the interpretation and the potential mechanistic claims of the authors are incomplete in the current shape with the primary concerns regarding the contribution of Kdm1b or Kdm1a, as well as the specificity of the inhibitor and the antibody. The work will be of interest to researchers interested in epigenetic reprogramming.

Reviewed by eLife

Massively Parallel Polyribosome Profiling Reveals Translation Defects of Human Disease-Relevant UTR Mutations

1. Wei-Ping Li
2. Jia-Ying Su
3. Yu-Chi Chang
4. Yun-Lin Wang
5. Hung-Lun Chiang
6. Yu-Tung Hsieh
7. Yi-Hsuan Chiang
8. Yen-Ling Ko
9. Bing-Jen Chiang
10. Cheng-Han Yang
11. Yen-Tsung Huang
12. Chien-Ling Lin

• Curated by eLife

  eLife assessment

  To elucidate the precise function of variants in the UTRs, the authors established and conducted a massively parallel poly(ribo)some profiling method to compare ribosome associations and effects of genetic variants. The approach and results are valuable, as this is a new approach to studying UTRs. However, the experimental and analytic validation seems to be incomplete, as the results are less robust than expected.

Reviewed by eLife

Deficiency in a special dynein DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice

1. Menglei Yang
2. Hafiz Muhammad Jafar Hussain
3. Manan Khan
4. Zubair Muhammad
5. Jianteng Zhou
6. Ao Ma
7. Xiongheng Huang
8. Jingwei Ye
9. Min Chen
10. Aoran Zhi
11. Tao Liu
12. Ranjha Khan
13. Asim Ali
14. Wasim Shah
15. Aurang Zeb
16. Nisar Ahmad
17. Huan Zhang
18. Bo Xu
19. Hui Ma
20. Qinghua Shi
21. Baolu Shi

• Curated by eLife

  eLife assessment

  This important study further validates DNAH12 as a causative gene for asthenoteratozoospermia and male infertility in humans and mice. The data supporting the notion that DNAH12 is required for proper axonemal development are generally convincing, although more experiments would solidify the conclusions. This work will interest reproductive biologists working on spermatogenesis and sperm biology, as well as andrologists working on male fertility.

Reviewed by eLife

fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans

1. Angela M Tuckowski
2. Safa Beydoun
3. Elizabeth S Kitto
4. Ajay Bhat
5. Marshall B Howington
6. Aditya Sridhar
7. Mira Bhandari
8. Kelly Chambers
9. Scott F Leiser

• Curated by eLife

  eLife assessment

  This important study offers convincing evidence that fmo-4 plays essential roles in established lifespan interventions and downstream of its paralog fmo-2, a beneficial advancement in our understanding of this enzyme family that underscores their importance in longevity and stress resistance. The study also suggests a connection between fmo-4 and dysregulation of calcium signalling. The authors' conclusions and interpretations were generally based on solid genetic methodology and evidence.

Reviewed by eLife

Systematic genetic characterization of the human PKR kinase domain highlights its functional malleability to escape a poxvirus substrate mimic

1. Michael J. Chambers
2. Sophia B. Scobell
3. Meru J. Sadhu

• Curated by eLife

  eLife assessment

  This valuable report describes the control of the activity of the RNA-activated protein kinase, PKR, by the Vaccinia virus K3 protein. A strength of the manuscript is the powerful combination of a yeast-based assay with high-throughput sequencing and its convincing experimental use to characterize large numbers of PKR variants. A minor weakness is that the scope of the screen conducted could still be extended, for example in terms of the segments of PKR included.

Reviewed by eLife