Molecular Biology

An ancient competition for the conserved branchpoint sequence influences physiological and evolutionary outcomes in splicing

1. Karen Larissa Pereira de Castro
2. Jose M Abril
3. Kuo-Chieh Liao
4. Haiping Hao
5. John Paul Donohue
6. William K Russell
7. W Samuel Fagg

• Curated by eLife

  eLife Assessment

  This important manuscript provides insights into the competition between Splicing Factor 1 (SF1) and Quaking (QKI) for binding at the ACUAA branch point sequence in a model intron, regulating exon inclusion. The study employs rigorous transcriptomic, proteomic, and reporter assays, with both mammalian cell culture and yeast models. Nevertheless, while the data are convincing, broadening the analysis to additional exons and narrowing the manuscript's title to better align with the experimental scope would strengthen the work.

Reviewed by eLife

Saccharomyces cerevisiae Rev7 promotes non-homologous end-joining by blocking Mre11 nuclease and Rad50’s ATPase activities and homologous recombination

1. Sugith Badugu
2. Kshitiza Mohan Dhyani
3. Manoj Thakur
4. Kalappa Muniyappa

• Curated by eLife

  eLife Assessment

  This manuscript reports important data providing evidence that a 42 amino acid region of Rev7 is necessary and sufficient for interaction with the Rad50-Mre11-Xrs2 complex in budding yeast. The authors conclude that Rev7 inhibits the Rad50 ATPase and the Mre11 nuclease with the exception of ssDNA exonuclease activity. The convincing data largely support the conclusions, although the effect of Rev7 on homologous recombination is less well documented and the observed effect on resection is moderate. Specifically, the result that the Rev7 C-terminal truncation lacking the 42 amino acid region still suppresses homologous recombination is unexpected and unexplained.

Reviewed by eLife

Human immunodeficiency virus-1 induces host genomic R-loops and preferentially integrates its genome near the R-loop regions

1. Kiwon Park
2. Dohoon Lee
3. Jiseok Jeong
4. Sungwon Lee
5. Sun Kim
6. Kwangseog Ahn

• Curated by eLife

  eLife Assessment

  This study presents two main findings regarding HIV-1 genomic integration. The first, based on convincing evidence in primary cell models, is that HIV-1 induces R loop formation, though the viral driver of this process remains undefined. The second, based on model cell systems with limited physiological relevance to HIV-1, is that a portion of HIV-1 genomes integrates in the vicinity of where R loops form. This finding has the potential to offer fundamental insight into HIV-1 integration, but the strength of the presented evidence was viewed as incomplete and needing additional validation by more direct experimental methods in order to understand what the mechanistic relationship between the formation of R loops and HIV-1 integration is.

Reviewed by eLife

Ensemble refinement of mismodeled cryo-EM RNA structures using all-atom simulations

1. Elisa Posani
2. Pavel Janoš
3. Daniel Haack
4. Navtej Toor
5. Massimiliano Bonomi
6. Alessandra Magistrato
7. Giovanni Bussi

Reviewed by PREreview

Genetic stability of Mycobacterium smegmatis under the stress of first-line antitubercular agents

1. Dániel Molnár
2. Éva Viola Surányi
3. Tamás Trombitás
4. Dóra Füzesi
5. Rita Hirmondó
6. Judit Toth

• Curated by eLife

  eLife Assessment

  This useful study reports on the impact of antibiotic pressure on the genomic stability of the mc2155 strain of Mycobacterium smegmatis, a model for Mycobacterium tuberculosis. The findings of the study indicate that exposure to antibiotics did not lead to the development of new adaptive mutations in controlled laboratory environments, challenging the notion that antibiotic resistance arises from drug-induced microevolution. The genomic analysis provides detailed insights into the stability of M. smegmatis following exposure to standard TB treatment antibiotics, and the evidence suggesting that antibiotic pressure does not contribute to the emergence of new adaptive mutations is solid.

Reviewed by eLife

Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity

1. Jisun So
2. Olivia Strobel
3. Jamie Wann
4. Kyungchan Kim
5. Avishek Paul
6. Dominic J Acri
7. Luke C Dabin
8. Jungsu Kim
9. Gang Peng
10. Hyun Cheol Roh

• Curated by eLife

  eLife Assessment

  So et al. present an optimized protocol for single-nuclei RNA sequencing of adipose tissue in mice, ensuring better RNA quality and nuclei integrity. The authors use this protocol to explore the cellular landscape in both lean and diet-induced obese mice, identifying a dysfunctional hypertrophic adipocyte subpopulation linked to obesity. The data analyses are solid, and the findings are supported by the evidence presented. This study provides valuable information for the field of adipose tissue biology and will be particularly helpful for researchers using single-nuclei transcriptomics in various tissues.

Reviewed by eLife

Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways

1. Anna Herrmannová
2. Jan Jelínek
3. Klára Pospíšilová
4. Farkas Kerényi
5. Tomáš Vomastek
6. Kathleen Watt
7. Jan Brábek
8. Mahabub Pasha Mohammad
9. Susan Wagner
10. Ivan Topisirovic
11. Leoš Shivaya Valášek

• Curated by eLife

  eLife Assessment

  This study demonstrates mRNA-specific regulation of translation by subunits of the eukaryotic initiation factor complex 3 (eIF3) using convincing methods, data, and analyses. The investigations have generated important information that will be of interest to biologists studying translation regulation. However, the physiological significance of the gene expression changes that were observed is not clear.

Reviewed by eLife

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