Genetics

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. The work is of substantial benefit for our understanding of this enzyme family, underscoring their importance in longevity and stress resistance. The study also suggests a connection between fmo-4 and dysregulation of calcium signalling, with conclusions and interpretations based on solid genetic methodology and evidence.

Reviewed by eLife

Bystander activation across a TAD boundary supports a cohesin-dependent hub-model for enhancer function

1. Iain Williamson
2. Katy A. Graham
3. Hannes Becher
4. Robert E. Hill
5. Wendy A. Bickmore
6. Laura A. Lettice

Reviewed by Review Commons

Mettl5 coordinates protein production and degradation of PERIOD to regulate sleep in Drosophila

1. Xiaoyu Wu
2. Xingzhuo Yang
3. Tiantian Fu
4. Yikang S Rong
5. Juan Du

• Curated by eLife

  eLife Assessment

  In this manuscript, the authors present useful findings demonstrating that the RNA modification enzyme Mettl5 regulates sleep in Drosophila. Through transcriptome- and proteome-wide analyses, the authors identified downstream targets affected in heterozygous mutants and proposed that Mettl5 regulates the translation and degradation of clock genes to maintain normal sleep function. However, the mechanisms by which Mettl5 achieves these functions, and whether they are direct or indirect, remain incomplete and would benefit from further analysis.

Reviewed by eLife

Multiplexed assays of human disease-relevant mutations reveal UTR dinucleotide composition as a major determinant of RNA stability

1. Jia-Ying Su
2. Yun-Lin Wang
3. Yu-Tung Hsieh
4. Yu-Chi Chang
5. Cheng-Han Yang
6. YoonSoon Kang
7. Yen-Tsung Huang
8. Chien-Ling Lin

• Curated by eLife

  eLife Assessment

  This valuable study combines massively parallel reporter assays and regression analysis to identify sequence features in untranslated regions contributing to the stability of in vitro transcribed mRNA delivered to cells. The strength of evidence presented is solid, although some points about half-life measurements and the relevance of identified sequence features to native transcript stability will inform future discussion surrounding the present study. Taken together, the work will be of interest to a broad swath of colleagues studying post-transcriptional gene regulation and especially to those using massively parallel reporter assays.

Reviewed by eLife

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility

1. Sophie Debaenst
2. Tamara Jarayseh
3. Hanna De Saffel
4. Jan Willem Bek
5. Matthieu Boone
6. Ivan Josipovic
7. Pierre Kibleur
8. Ronald Y Kwon
9. Paul J Coucke
10. Andy Willaert

• Curated by eLife

  eLife Assessment

  The paper presents a streamlined new approach for functional validation of genes known to underlie fragile bone disorders in a relatively high throughput, using CRISPR-mediated knockouts and a number of phenotypic assessments in zebrafish. Convincing data demonstrate the feasibility and validity of this approach, which presents an important tool for rapid functional validation of candidate gene(s) associated with heritable bone diseases identified from genetic studies.

Reviewed by eLife

Intergenerational transport of double-stranded RNA in C. elegans can limit heritable epigenetic changes

1. Nathan M Shugarts Devanapally
2. Aishwarya Sathya
3. Andrew L Yi
4. Winnie M Chan
5. Julia A Marre
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 and the revision contain generally solid support for the central findings of the work. These findings will be of interest to those working in the germline epigenetic inheritance field.

Reviewed by eLife

DYRK1A kinase triplication is the major cause of Otitis Media in Down Syndrome

1. Hilda Tateossian
2. Amy Southern
3. Pratik Vikhe
4. Eva Lana-Elola
5. Sheona Watson-Scales
6. Dorota Gibbins
7. Debbie Williams
8. Thomas Purnell
9. Philomena Mburu
10. Andrew Parker
11. Dominic P Norris
12. Regie Lyn P Santos-Cortez
13. Brian W Herrmann
14. Sara Wells
15. Heena V Lad
16. Elizabeth MC Fisher
17. Victor LJ Tybulewicz
18. Steve DM Brown

• Curated by eLife

  eLife Assessment

  This study addresses fundamental questions surrounding otitis media effusion in Down syndrome, identifying DYRK1A as a key gene involved in the condition. The findings are compelling, highlighting DYRK1A as a promising therapeutic target for addressing hearing loss in patients with Down syndrome.

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 useful study highlights the largely redundant role of the decapping activators Edc3 and Scd6 in orchestrating post-transcriptional programs to modulate metabolic responses to nutrients in yeast. The authors provide solid evidence for their conclusions, employing a variety of mutants in conjunction with a battery of transcriptome-wide analyses. This study could be further strengthened by direct biochemical validation of the functional interactions observed by systems biology approaches.

Reviewed by eLife

Reported transgenerational responses to Pseudomonas aeruginosa in Caenorhabditis elegans are not robust

1. Daniel Patrick Gainey
2. Andrey V Shubin
3. Craig P Hunter

• Curated by eLife

  eLife Assessment

  This important study reports numerous attempts to replicate reports on transgenerational inheritance of a learned behavior – pathogen avoidance – in C. elegans. While the authors observe parental effects that are limited to a single generation (also called intergenerational inheritance), the authors failed to find evidence for transmission over multiple generations, or transgenerational inheritance. The experiments presented are meticulously described, making for compelling evidence that in the authors' hands transgenerational inheritance cannot be observed. There remains the possibility that different assay setups explain the failure to reproduce previous observations, although the authors present data suggesting that details of the assay are not that significant. There also remains the possibility that differences in culture conditions or lab environment explain the failure to reproduce previous observations, with updates to the paper having further reduced the probability that this applies here. Even if this were the case, it would imply that the original experimental paradigm was dependent on a very specific context. Given the prominence of the original reports of transgenerational inheritance, the present study is of broad interest to anyone studying genetics, epigenetics, or learned behavior.

  [As also pointed out by the authors of this study, the authors of the original reports have provided a response on bioRxiv (DOI: https://doi.org/10.1101/2025.01.21.634111).]

Reviewed by eLife

An H3-K9-me-independent binding of Swi6/HP1 to siRNA-DNA hybrids initiates heterochromatin assembly at cognate dg-dh repeats in Fission Yeast

1. Jyotsna Kumar
2. Swati Haldar
3. Neelima Gupta
4. Viney Kumar
5. Manisha Thakur
6. Keerthivasan Raanin Chandradoss
7. Debarghya Ghose
8. Dipak Dutta
9. Kuljeet Singh Sandhu
10. Jagmohan Singh

• Curated by eLife

  eLife Assessment

  This study aims to investigate the RNA binding activities of a conserved heterochromatin protein (Swi6) and proposes an entirely new model for how heterochromatin formation is initiated in fission yeast. While the concept is interesting, the data provided are inadequate, both for support of the claims regarding the new RNA binding activities and for support of the new model. The paper requires extensive editing as well as the inclusion of numerous experiments with appropriately controlled conditions.

Reviewed by eLife