Molecular Biology

An anciently diverged family of RNA binding proteins maintain correct splicing of a class of ultra-long exons through cryptic splice site repression

1. Chileleko Siachisumo
2. Sara Luzzi
3. Saad Aldalaqan
4. Gerald Hysenaj
5. Caroline Dalgliesh
6. Kathleen Cheung
7. Matthew R Gazzara
8. Ivaylo D Yonchev
9. Katherine James
10. Mahsa Kheirollahi Chadegani
11. Ingrid E Ehrmann
12. Graham R Smith
13. Simon J Cockell
14. Jennifer Munkley
15. Stuart A Wilson
16. Yoseph Barash
17. David J Elliott

• Curated by eLife

  eLife assessment

  This important paper addresses the process by which cryptic splice sites that occur randomly in exons are ignored by the splicing machinery. Integrating state-of- the-art genome-wide approaches such as CLIP-seq with the study of individual examples, this study convincingly implicates members of RBMX family of RNA binding proteins in such cryptic splice site suppression and showcases its importance for the fidelity of expression of genes with very large exons.

Reviewed by eLife

An intestinal Sir2-HSF1-ATGL1 pathway regulates lipolysis in C. elegans

1. Milán Somogyvári
2. Saba Khatatneh
3. Gábor Hajdú
4. Bar Sotil
5. József Murányi
6. Csaba Sőti

Reviewed by Review Commons

An in vitro approach reveals molecular mechanisms underlying endocrine disruptor-induced epimutagenesis

1. Jake D Lehle
2. Yu-Huey Lin
3. Amanda Gomez
4. Laura Chavez
5. John R McCarrey

• Curated by eLife

  eLife assessment

  This important study, characterizing the epigenetic and transcriptomic response of a variety of cell types representative of somatic, germline, and pluripotent cells to BPS, reveals the cell type-specific changes in DNA methylation and the relationship with the genome sequence. The findings are convincing and provide a basis for future analyses in vivo. This work should be of interest to biomedical researchers who work on epigenetic reprogramming and epigenetic inheritance.

Reviewed by eLife

A fine kinetic balance of interactions directs transcription factor hubs to genes

1. Samantha Fallacaro
2. Apratim Mukherjee
3. Puttachai Ratchasanmuang
4. Joseph Zinski
5. Yara I Haloush
6. Kareena Shankta
7. Mustafa Mir

Reviewed by preLights

ACE2-independent sarbecovirus cell entry is supported by TMPRSS2-related enzymes and reduces sensitivity to antibody-mediated neutralization

1. Lu Zhang
2. Hsiu-Hsin Cheng
3. Nadine Krüger
4. Bojan Hörnich
5. Luise Graichen
6. Alexander S. Hahn
7. Sebastian R. Schulz
8. Hans-Martin Jäck
9. Metodi V. Stankov
10. Georg M.N. Behrens
11. Marcel A. Müller
12. Christian Drosten
13. Onnen Mörer
14. Martin Sebastian Winkler
15. ZhaoHui Qian
16. Stefan Pöhlmann
17. Markus Hoffmann

Reviewed by Review Commons

Multi-protein chimeric antigens, a novel combined approach for efficiently targeting and blocking the blood stage of Plasmodium falciparum

1. Bhagyashree Deshmukh
2. Dhruv Khatri
3. Sanjay Kumar Kochar
4. Chaitanya Athale
5. Krishanpal Karmodiya

Reviewed by Review Commons

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

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

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