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

A whole-organism landscape of X-inactivation in humans

1. Björn Gylemo
2. Maike Bensberg
3. Colm E. Nestor

• Curated by eLife

  eLife Assessment

  The study provides a valuable analysis of escape from X-inactivation based on three rare female GTEX-donors with non-mosaic X-inactivation. The methods and analyses broadly support the author's claims, although some additional explanation could be helpful. Their data are more comprehensive than those presented previously and add significant weight to evidence for which genes are inactivated or escape from X inactivation in humans. However, without further experimentation the overall study unfortunately remains incomplete in its current form.

Reviewed by eLife

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes

1. Stephen A Banse
2. Christine A Sedore
3. Anna L Coleman-Hulbert
4. Erik Johnson
5. Brian Onken
6. David Hall
7. Erik Segerdell
8. E Grace Jones
9. Yuhua Song
10. Hadley Osman
11. Jian Xue
12. Elena Battistoni
13. Suzhen Guo
14. Anna C Foulger
15. Madhuri Achanta
16. Mustafa Sheikh
17. Theresa Fitzgibbon
18. John H Willis
19. Gavin C Woodruff
20. Monica Driscoll
21. Gordon J Lithgow
22. Patrick C Phillips

• Curated by eLife

  eLife Assessment

  This important study explores the power of computational methods to predict lifespan-extending small molecules, demonstrating that while these methods significantly increase hit rates, experimental validation remains essential. The study uses all-trans retinoic acid in Caenorhabditis elegans as a model, providing genetic and transcriptomic insights into its longevity effects. The data are compelling in describing a robust, computationally informed screening process for discovering compounds that extend lifespan in this species.

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