Genetics

Acute opioid responses are modulated by dynamic interactions of Oprm1 and Fgf12

1. Paige M Lemen
2. Yanning Zuo
3. Alexander S Hatoum
4. Price E Dickson
5. Guy Mittleman
6. Arpana Agrawal
7. Benjamin C Reiner
8. Wade Berrettini
9. David G Ashbrook
10. Mustafa Hakan Gunturkun
11. Xusheng Wang
12. Megan K Mulligan
13. Caleb J Browne
14. Eric J Nestler
15. Francesca Telese
16. Robert W Williams
17. Hao Chen

• Curated by eLife

  eLife Assessment

  This study integrates large-scale behavioral, genetic, and molecular analyses in animal models to investigate morphine response. Utilizing high-quality, time-series Quantitative Trait Loci (QTL) mapping, the work provides compelling evidential support for novel, time-dependent genetic interactions (epistasis). A fundamental result of this rigorous analysis is the discovery of a novel Oprm1-Fgf12-MAPK signaling pathway, which offers new insights into the mechanisms of opioid sensitivity.

Reviewed by eLife

Nucleosome Positioning Shapes Cryptic Antisense Transcription

1. Jian Yi Kok
2. Zachary H. Harvey
3. Elin Axelsson
4. Frédéric Berger

Reviewed by Review Commons

Redox Dyshomeostasis Links Renal and Neuronal Dysfunction in Drosophila Models of Gaucher and Parkinson’s Disease

1. Alexander J Hull
2. Magda L Atilano
3. Kerri J Kinghorn

• Curated by eLife

  eLife Assessment

  This is a valuable manuscript that reframes Gaucher's disease pathology through the analysis of renal health, using a Drosophila model mutant for glucocerebrosidase (GBA1). The authors provide physiological and cellular data showing that renal dysfunction may be a critical disease-modifying feature. This work broadens the field's focus beyond the nervous system to include systemic ionic regulation as a potential contributor to disease initiation and progression. The genetic and experimental approaches are solid and offer a rationale for investigating analogous dysfunction in human tissues; however, several claims extend beyond the presented evidence and would benefit from additional experimental support to fully support the conclusions.

Reviewed by eLife

Abundant Parent-of-origin Effect eQTL: The Framingham Heart Study

1. Yongtao Guan
2. Tianxiao Huan
3. Daniel Levy

• Curated by eLife

  eLife Assessment

  This important study provides a systematic investigation of parent-of-origin (POE) effects on gene expression using large trio-based data from the Framingham Heart Study, uncovering thousands of potentially novel associations. While the findings are potentially significant, the statistical support for classifying POE eQTLs and some downstream analyses is incomplete, and more stringent re-analysis is needed. With such revisions, the work would serve as a foundation for advancing understanding of POEs and their role in gene regulation.

Reviewed by eLife

BICC1 Interacts with PKD1 and PKD2 to Drive Cystogenesis in ADPKD

1. Uyen Tran
2. Andrew J Streets
3. Devon Smith
4. Eva Decker
5. Annemarie Kirschfink
6. Lahoucine Izem
7. Jessie M Hassey
8. Briana Rutland
9. Manoj K Valluru
10. Jan Hinrich Bräsen
11. Elisabeth Ott
12. Daniel Epting
13. Tobias Eisenberger
14. Albert CM Ong
15. Carsten Bergmann
16. Oliver Wessely

• Curated by eLife

  eLife Assessment

  This study presents valuable findings regarding the basic molecular pathways leading to the cystogenesis of Autosomal Dominant Polycystic Kidney Disease, suggesting BICC1 functions as both a minor causative gene for PKD and a modifier of PKD severity. Solid data were supplied to show the functional and structural interactions between BICC-1 and PKD2 and their relevance to the pathogenesis of ADPKD, although the characterization of such interactions remains to be developed further and the clinical relevance is currently unclear.

Reviewed by eLife

Independent validation of transgenerational inheritance of learned pathogen avoidance in Caenorhabditis elegans

1. Aalimah Akinosho
2. Joseph Alexander
3. Kyle Floyd
4. Andres Gabriel Vidal-Gadea

• Curated by eLife

  eLife Assessment

  This valuable study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. A recent study questioned whether transgenerational inheritance in this paradigm lacks robustness. The authors of this study have worked independently of the group that reported the original phenomenon and also independently of the group that challenged the original report. With solid data, this study independently validates findings previously reported by the Murphy group, confirming that the paradigm is reproducible elsewhere. The reviewers also appreciated the information on reagent sources used by different groups. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

Reviewed by eLife

Decapping activators Edc3 and Scd6 act redundantly with Dhh1 in post-transcriptional repression of starvation-induced pathways

1. Rakesh Kumar
2. Fan Zhang
3. Shreyas Niphadkar
4. Chisom Onu
5. Anil Kumar Vijjamarri
6. Miriam L Greenberg
7. Sunil Laxman
8. Alan G Hinnebusch

• Curated by eLife

  eLife Assessment

  This important study reports on the redundant roles of the decapping activators Edc3 and Scd6 in orchestrating post-transcriptional programs to modulate metabolic responses to nutrients in yeast. The authors employed mutagenesis studies in conjunction with a battery of transcriptome-wide analyses to provide convincing evidence supporting their conclusions. Considering the broad implications of post-transcriptional regulation of gene expression, this study will be of interest across a variety of biomedical disciplines ranging from biochemistry and molecular and cellular biology to those specializing in studying various pathologies.

Reviewed by eLife

Microbiota/gut/neuron axis promotes Drosophila ageing via Acetobacter, Tachykinin, and TkR99D

1. Diana Marcu
2. David R Sannino
3. Anthony J Dornan
4. Rita Ibrahim
5. Atharv Kapoor
6. Miriam Wood
7. Adam J Dobson

Reviewed by Review Commons

Mapping of in vivo cleavage sites uncovers a major role for yeast RNase III in regulating protein-coding genes

1. Lee-Ann Notice-Sarpaning
2. Mathieu Catala
3. Catherine Stuart
4. Sherif Abou Elela
5. Ambro van Hoof

• Curated by eLife

  eLife Assessment

  This valuable study expands the inventory of polyadenylated RNAs cleaved by the double-stranded RNA endonuclease Rnt1 in budding yeast, using solid methodology based on high-throughput sequencing. Previous studies had anecdotally discovered mRNA substrates, and this global characterization is comprehensive with multiple complementary controls. This study sets the stage for deeper investigations into the biological function of Rnt1 and substrate cleavage.

Reviewed by eLife

Importance of higher-order epistasis in protein sequence-function relationships

1. Palash Sethi
2. Juannan Zhou

• Curated by eLife

  eLife Assessment

  In this important work, the authors present a new transformer-based neural network designed to isolate and quantify higher-order epistasis in protein sequences. They provide solid evidence that higher-order epistasis can play key roles in protein function. This work will be of interest to the communities interested in modeling biological sequence data and understanding mutational effects.

Reviewed by eLife