Molecular Biology

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease

1. Robyn D Moir
2. Emilio Merheb
3. Violeta Chitu
4. E Richard Stanley
5. Ian M Willis

• Curated by eLife

  eLife Assessment

  This study provides important insights into the mechanistic basis of neurological manifestations of RNA polymerase III-related disease by creating a mutant mouse to dissect transcriptional changes. The data provide compelling evidence for disease progression initiated by a global reduction in tRNA levels leading to integrated stress and innate immune responses and neuronal loss. The work will be of interest to those engaged in the study of chromosome biology, developmental biology and neurodegeneration.

Reviewed by eLife

RNA tertiary structure and conformational dynamics revealed by BASH MaP

1. Maxim Oleynikov
2. Samie R Jaffrey

• Curated by eLife

  eLife Assessment

  This important work substantially advances our understanding of RNA structure analysis by introducing an innovative method that extends DMS probing to include guanosine residues, thereby enhancing our ability to detect complex tertiary interactions. The evidence supporting the conclusions is compelling, with detailed analyses demonstrating the method's capacity to differentiate structural contexts and improve RNA structure predictions. This work will be of broad interest to RNA structural biology, biochemistry, and biophysics researchers.

Reviewed by eLife

UBR4 regulates a MetAP2-dependent Arg/N-degron pathway

1. Evan J. Morrison
2. Emma Horton
3. Olivia S. Rissland

Reviewed by Life Science Editors Foundation

Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis

1. Célia Alecki
2. Javeria Rizwan
3. Phuong Le
4. Suleima Jacob-Tomas
5. Mario Fernandez-Comaduran
6. Morgane Verbrugghe
7. Jia Ming Stella Xu
8. Sandra Minotti
9. James Lynch
10. Jeetayu Biswas
11. Tad Wu
12. Heather Durham
13. Gene W. Yeo
14. Maria Vera

Reviewed by Life Science Editors Foundation

ORMDL3 restrains type-I interferon signaling and anti-tumor immunity by promoting RIG-I degradation

1. Qi Zeng
2. Chen Yao
3. Shimeng Zhang
4. Yizhi Mao
5. Jing Wang
6. Ziyang Wang
7. Chunjie Sheng
8. Shuai Chen

• Curated by eLife

  eLife Assessment

  The research has the potential to be a valuable addition to the field, and the conclusions are solid, but there is a need for more reproducible data to address existing discrepancies and enhance its impact.

Reviewed by eLife

Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms

1. Jessica E Schwarz
2. Antonijo Mrčela
3. Nicholas F Lahens
4. Yongjun Li
5. Cynthia T Hsu
6. Gregory Grant
7. Carsten Skarke
8. Shirley L Zhang
9. Amita Sehgal

• Curated by eLife

  eLife Assessment

  The authors tested the hypothesis that age-dependent factors in human sera affect the core circadian clock or its outputs in cultured fibroblasts, and they provide compelling evidence that genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions, genes associated with oxidative phosphorylation and Alzheimer's Disease lose rhythmicity in the aged condition, while the expression of cycling genes associated with cholesterol biosynthesis increase in the cells entrained with old serum. Together, the findings suggest that yet to be identified age-dependent blood-borne factors affect circadian rhythms in the periphery. The paper provides fundamental insights and a possible explanation for previous observations showing that circadian gene expression in peripheral tissues tends to dampen or phase-shift with age.

Reviewed by eLife

Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions

1. Ting-Wen Chen
2. Hsiao-Wei Liao
3. Michelle Noble
4. Jing-Yi Siao
5. Yu-Hsuan Cheng
6. Wei-Chung Chiang
7. Yi-Tzu Lo
8. Chung-Te Chang

• Curated by eLife

  eLife Assessment

  This study attempts to understand the functional roles of the human DCP1 paralogs in regulating RNA decay by DCP2. Using a combination of cellular-based assays and in vitro assays, the authors conclude that DCP1a/b plays a role in regulating DCP2 activity. While this revised version presents some new and interesting observations on human DCP1, the underlying data to support its claims remain incomplete. Overall, these results will be useful to the RNA community.

Reviewed by eLife

Description of a novel extremophile green algae, Chlamydomonas pacifica, and its potential as a biotechnology host

1. Joao Vitor Dutra Molino
2. Aaron Oliver
3. Harish Sethuram
4. Kalisa Kang
5. Barbara Saucedo
6. Crisandra Jade Diaz
7. Abhishek Gupta
8. Lee Jong Jen
9. Yasin Torres-tiji
10. Nora Hidasi
11. Amr Badary
12. Hunter Jenkins
13. Francis J. Fields
14. Stephen Mayfield

Reviewed by Arcadia Science

Structure of human PIEZO1 and its slow inactivating channelopathy mutants

1. Yuanyue Shan
2. Xinyi Guo
3. Mengmeng Zhang
4. Meiyu Chen
5. Ying Li
6. Mingfeng Zhang
7. Duanqing Pei

• Curated by eLife

  eLife Assessment

  This useful manuscript shows a set of interesting data including the first cryo-EM structures of human PIEZO1 as well as structures of disease-related mutants in complex with the regulatory subunit MDFIC, which generate different inactivation phenotypes. The molecular basis of PIEZO channel inactivation is of great interest due to its association with several pathologies. This manuscript provides some structural insights that may help to ultimately build a molecular picture of PIEZO channel inactivation. While the structures are of use and clear conformational differences can be seen in the presence of the auxiliary subunit MDFIC, the strength of the evidence supporting the conclusions of the paper, especially the proposed role for pore lipids in inactivation, is incomplete and there is a lack of data to support them.

Reviewed by eLife

Nuclear Translocation of SIRT4 Mediates Deacetylation of U2AF2 to Modulate Renal Fibrosis Through Alternative Splicing-mediated Upregulation of CCN2

1. Guangyan Yang
2. Jiaqing Xiang
3. Xiaoxiao Yang
4. Xiaomai Liu
5. Yanchun Li
6. Lixing Li
7. Lin Kang
8. Zhen Liang
9. Shu Yang

• Curated by eLife

  eLife Assessment

  This study demonstrates a novel role for SIRT4; a mitochondrial deacetylase, shown to translocate into nuclei where it regulates RNA alternative splicing by modulating U2AF2 and the gene expression of CCN2 in tubular cells in response to TGF-β. This fundamental work substantially advances our understanding of kidney fibrosis development and offers a potential therapeutic approach. The evidence supporting the conclusions of a SIRT4-U2AF2-CCN2 axis activated by TGF-β is compelling and adds a new layer of complexity to the pathogenesis of chronic kidney disease.

Reviewed by eLife