Molecular Biology

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

Time-resolved mitochondrial-focused screening identifies regulatory components of oxidative metabolism

1. Marcos Zamora-Dorta
2. Sara Laine-Menéndez
3. David Abia
4. Pilar González-García
5. Luis C. López
6. Paula Fernández-Montes Díaz
7. Enrique Calvo
8. Jesús Vázquez
9. José Antonio Enríquez
10. Eduardo Balsa

Reviewed by Arcadia Science

Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain

1. Gabriella O Estevam
2. Edmond M Linossi
3. Christian B Macdonald
4. Carla A Espinoza
5. Jennifer M Michaud
6. Willow Coyote-Maestas
7. Eric A Collisson
8. Natalia Jura
9. James S Fraser

• Curated by eLife

  eLife assessment

  This manuscript describes a deep mutational scanning study of the kinase domain of the MET receptor tyrosine kinase. The study yields an important catalog of essentially all possible deleterious mutations in this portion of the receptor., with convincing evidence. The manuscript will be of interest to researchers working in the field of receptor tyrosine kinases.

Reviewed by eLife

Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides

1. Meng-Hsuan Hsiao
2. Yang Miao
3. Zixing Liu
4. Konstantin Schütze
5. Nathachit Limjunyawong
6. Daphne Chun-Che Chien
7. Wayne Denis Monteiro
8. Lee-Shin Chu
9. William Morgenlander
10. Sahana Jayaraman
11. Sung-eun Jang
12. Jeffrey J. Gray
13. Heng Zhu
14. Xinzhong Dong
15. Martin Steinegger
16. H. Benjamin Larman

Reviewed by Arcadia Science

Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9

1. Joshua D Eaton
2. Jessica Board
3. Lee Davidson
4. Chris Estell
5. Steven West

• Curated by eLife

  eLife assessment

  The important study uses a new experimental method to provide compelling evidence on how sense- and anti-sense transcription is differentially regulated. The method described here can generally be used to study the alterations in transcription. This paper will be of interest to scientists working in the gene regulation community.

Reviewed by eLife

Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity

1. Christin Krause
2. Jan H Britsemmer
3. Miriam Bernecker
4. Anna Molenaar
5. Natalie Taege
6. Nuria Lopez-Alcantara
7. Cathleen Geißler
8. Meike Kaehler
9. Katharina Iben
10. Anna Judycka
11. Jonas Wagner
12. Stefan Wolter
13. Oliver Mann
14. Paul Pfluger
15. Ingolf Cascorbi
16. Hendrik Lehnert
17. Kerstin Stemmer
18. Sonja C Schriever
19. Henriette Kirchner

• Curated by eLife

  eLife assessment

  Building on on the observation of an increase in miR-182-5p in diabetic patients, the authors investigated the role of miR-182-5p and its target gene LRP6 in dysregulated glucose tolerance and fatty acid metabolism in obese type 2 diabetics. The use of human livers complemented by supporting data in mice and cells are strengths, but the evidence presented remains incomplete. The findings provide valuable insights into the role of miRNAs in the regulation of liver metabolism and insulin sensitivity in individuals with diabetes and fatty liver disease.

Reviewed by eLife

The specific AMPK activator A-769662 ameliorates pathological phenotypes following mitochondrial DNA depletion

1. Gustavo Carvalho
2. Bruno Repolês
3. Tran V.H. Nguyen
4. Josefin M.E. Forslund
5. Farahnaz Ranjbarian
6. Isabela C. Mendes
7. Micol Falabella
8. Mara Doimo
9. Sjoerd Wanrooij
10. Robert D.S. Pitceathly
11. Anders Hofer
12. Paulina H. Wanrooij

Reviewed by Review Commons

Punctuated and continuous structural diversity of S-layers across the prokaryotic tree of life

1. Edward Johnston
2. Buse Isbilir
3. Vikram Alva
4. Tanmay A.M. Bharat
5. Jonathan P. K. Doye

Reviewed by Arcadia Science

Enhancer cooperativity can compensate for loss of activity over large genomic distances

1. Henry F. Thomas
2. Songjie Feng
3. Felix Haslhofer
4. Marie Huber
5. María García Gallardo
6. Vincent Loubiere
7. Daria Vanina
8. Mattia Pitasi
9. Alexander Stark
10. Christa Buecker

Reviewed by preLights