Genetics

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

1. Jacob W Klemm
2. Chloe Van Hazel
3. Robin E Harris

• Curated by eLife

  eLife Assessment

  This manuscript reports fundamental discoveries on how necrotic cells contribute to organ regeneration through apoptotic signalling to produce cells with non-lethal apoptotic caspase activity that contribute to the regenerated tissue. These findings will be of broad interest to those who study wound repair and tissue regeneration. The strength of the evidence is solid and has been improved in the revised version.

Reviewed by eLife

The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition

1. Gülnihal Kavaklioglu
2. Alexandra Podhornik
3. Terezia Vcelkova
4. Jelena Marjanovic
5. Mirjam A Beck
6. Trinh Phan-Canh
7. Theresia Mair
8. Claudia Miccolo
9. Aleksej Drino
10. Mirko Doni
11. Gerda Egger
12. Susanna Chiocca
13. Miha Modic
14. Christian Seiser

• Curated by eLife

  eLife Assessment

  This important paper reports functional interactions between L1TD1, an RNA binding protein (RBP), and its ancestral LINE-1 retrotransposon which is not modulated at the translational level. The evidence for the association between L1TD1 and LINE-1 ORF1p is solid. The work implies that the transposon-derived RNA binding protein in the human genome can interact with the ancestral transposable element from which this protein was initially derived. This work spurs interesting questions for cancer types, where LINE1 and L1TD1 are aberrantly expressed.

Reviewed by eLife

Deficiency in 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. Ali Asim
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 fundamental study further validates DNAH12 as a causative gene for asthenoteratozoospermia and male infertility in both humans and mice. Compelling evidence supports the notion that DNAH12 is essential for proper axonemal development. This work will be of interest to reproductive biologists studying spermatogenesis and sperm biology, as well as andrologists focusing on male fertility.

Reviewed by eLife

Impact of liver-specific survival motor neuron (SMN) depletion on central nervous system and peripheral 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 an important 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 with convincing evidence supporting their claims.

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. 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

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