Molecular Biology

Association with TFIIIC limits MYCN localisation in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA polymerase II

1. Raphael Vidal
2. Eoin Leen
3. Steffi Herold
4. Mareike Müller
5. Daniel Fleischhauer
6. Christina Schülein-Völk
7. Dimitrios Papadopoulos
8. Isabelle Röschert
9. Leonie Uhl
10. Carsten P Ade
11. Peter Gallant
12. Richard Bayliss
13. Martin Eilers
14. Gabriele Büchel

• Curated by eLife

  eLife assessment

  This study presents the valuable finding that TFIIIC interacts with MYCN to regulate RNA polymerase II dynamics by dissecting its impact on 3D chromatin architecture. Authors provide convincing evidence that MYCN and TFIIIC show long-range chromatin contacts, and that the expression of each protein limits the function of the other. The notion emerges that TFIIIC helps MYCN to maintain output at promoters while decreasing less productive associations at larger more extensively connected chromatin hubs. The paper is of interest to molecular biologists working on MYCN-dependent regulation of gene expression.

Reviewed by eLife

Changes in local mineral homeostasis facilitate the formation of benign and malignant testicular microcalcifications

1. Ida Marie Boisen
2. Nadia Krarup Knudsen
3. John Erik Nielsen
4. Ireen Kooij
5. Mathilde Louise Bagger
6. Jovana Kaludjerovic
7. Peter J. O’ Shaughnessy
8. Peter W. Andrews
9. Noriko Ide
10. Birgitte Grønkær Toft
11. Anders Juul
12. Arnela Mehmedbašić
13. Anne Jørgensen
14. Lee B. Smith
15. Richard W. Norman
16. Ewa Rajpert-De Meyts
17. Beate Lanske
18. Martin Blomberg Jensen

• Curated by eLife

  eLife assessment

  This valuable study reports data showing the link between a disruption in testicular mineral (phosphate) homeostasis, FGF23 expression, and Sertoli cell dysfunction. The data supporting the conclusion remains incomplete. This work will be of interest to biomedical researchers working on testis biology and male infertility.

Reviewed by eLife

Comprehensive Phenotyping of Extracellular Vesicles in Blood of Healthy Humans – Insights into Cellular Origin and Biological Variability

1. Marija Holcar
2. Ivica Marić
3. Tobias Tertel
4. Katja Goričar
5. Urška Čegovnik Primožič
6. Darko Černe
7. Bernd Giebel
8. Metka Lenassi

Reviewed by Arcadia Science

Deciphering the actin structure-dependent preferential cooperative binding of cofilin

1. Kien Xuan Ngo
2. Huong T Vu
3. Kenichi Umeda
4. Minh-Nhat Trinh
5. Noriyuki Kodera
6. Taro Uyeda

• Curated by eLife

  eLife assessment

  In this manuscript the authors present high-speed atomic force microscopy (HSAFM) to analyze real-time structural changes in actin filaments induced by cofilin binding. This important study enhances our understanding of actin dynamics which plays a crucial role in a broad spectrum of cellular activities based on solid experimental evidence. Some technical questions, however, remain, making the data interpretation incomplete.

Reviewed by eLife

PDGFRα signaling regulates Srsf3 transcript binding to affect PI3K signaling and endosomal trafficking

1. Thomas E. Forman
2. Marcin P. Sajek
3. Eric D. Larson
4. Neelanjan Mukherjee
5. Katherine A. Fantauzzo

• Curated by eLife

  eLife assessment

  This fundamental work provides new mechanistic insight into the regulation of PDGF signaling through splicing controls. The evidence is compelling to demonstrate the involvement of Srsf3, an RNA-binding protein, in this new mechanism. The work will be of broad interest to developmental biologists in general and molecular biologists/biochemists in the field of growth factor signaling and RNA splicing.

Reviewed by eLife

Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency

1. Zach Hensel

• Curated by eLife

  eLife assessment

  This short manuscript uses mutation counts in phylogenies of millions of SARS-CoV-2 genomes to show that mutation rates systematically differ between regions that are paired or unpaired in the predicted RNA secondary structure of the viral genome. Such an effect of pairing state is not unexpected, but its systematic demonstration using millions of viral genomes is valuable and convincing.

Reviewed by eLife

PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification

1. José Antonio Valer
2. Alexandre Deber
3. Marius Wits
4. Carolina Pimenta-Lopes
5. Marie-José Goumans
6. José Luis Rosa
7. Gonzalo Sánchez-Duffhues
8. Francesc Ventura

• Curated by eLife

  eLife assessment

  This study provides valuable insights by demonstrating that BYL719 is a promising therapeutic agent for the treatment of heterotopic ossification (HO), with inhibition of PI3Ka via BYL719 appearing to be a critical factor. However, the results of the study are incomplete because BYL719 affects multiple intracellular signaling pathways beyond PI3Ka, and it thus remains uncertain whether BYL719 attenuates HO exclusively through suppression of the PI3Ka pathway or through modulation of alternative signaling pathways. A detailed elucidation of the molecular mechanisms of action of BYL719 is essential for a thorough understanding of its effects.

Reviewed by eLife

Ribosomal composition affects the noncanonical translation and toxicity of polyglycine-containing proteins in fragile X-associated conditions

1. Katarzyna Tutak
2. Izabela Broniarek
3. Andrzej Zielezinski
4. Daria Niewiadomska
5. Anna Baud
6. Krzysztof Sobczak

• Curated by eLife

  eLife assessment

  In this study, Tutak and colleagues set out to identify factors that mediate Repeat Associated Non-AUG (RAN) translation of CGG repeats in the FMR1 mRNA which are implicated in toxic protein accumulation that underpins ensuing neurological pathologies. This is a useful article that suggests that RPS26 may be implicated in mediating the RAN translation of FMR1 mRNA. However, the evidence supporting the proposed mechanism is incomplete, since the provided data only partially support the authors' conclusion.

Reviewed by eLife

circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA

1. Trine Line Hauge Okholm
2. Andreas Bjerregaard Kamstrup
3. Morten Muhlig Nielsen
4. Anne Kruse Hollensen
5. Mette Laugesen Graversgaard
6. Matilde Helbo Sørensen
7. Lasse Sommer Kristensen
8. Søren Vang
9. Samuel S Park
10. Eugene Yeo
11. Lars Dyrskjøt
12. Jørgen Kjems
13. Jakob Skou Pedersen
14. Christian Kroun Damgaard

• Curated by eLife

  eLife assessment

  This work explores the role of one the most abundant circRNAs, circHIPK3, in bladder cancer cells, showing with convincing data that circHIPK3 depletion affects thousands of genes and that those downregulated (including STAT3) share an 11-mer motif with circHIPK3, corresponding to a binding site for IGF2BP2. The experiments demonstrate that circHIPK3 can compete with the downregulated mRNAs targets for IGF2BP2 binding and that IGF2BP2 depletion antagonizes the effect of circHIPK3 depletion by upregulating the genes containing the 11-mer. These important findings contribute to the growing recognition of the complexity of cancer signaling regulation and highlight the intricate interplay between circRNAs and protein-coding genes in tumorigenesis.

Reviewed by eLife

Artificially inserted strong promoter containing multiple G-quadruplexes induces long-range chromatin modification

1. Shuvra Shekhar Roy
2. Sulochana Bagri
3. Soujanya Vinayagamurthy
4. Avik Sengupta
5. Claudia Regina Then
6. Rahul Kumar
7. Sriram Sridharan
8. Shantanu Chowdhury

• Curated by eLife

  eLife assessment

  This valuable study demonstrates that genomic insertion of a G4-containing sequence can be sufficient to induce chromosome loops and alter gene expression. The evidence supporting the conclusions is convincing. Effects were shown by Hi-C as well as qPCR for chromatin modifications and expression, and the specificity of the effects was controlled by mutating the G4-containing sequence or treating with LNA probes to abolish G4 structure formation. The work will be of interest to researchers working on chromatin organization and gene regulation.

Reviewed by eLife