Biochemistry

Human DDX6 regulates translation and decay of inefficiently translated mRNAs

1. Ramona Weber
2. Chung-Te Chang

• Curated by eLife

  eLife assessment

  This study provides valuable findings that improve our understanding of the evolutionary conservation of the role of DDX6 in mRNA decay. The evidence supporting the authors' conclusions is convincing. This work will be of interest to molecular, cell biologists and biochemists, especially those studying RNA.

Reviewed by eLife

idh-1 neomorphic mutation confers sensitivity to vitamin B12 via increased dependency on one-carbon metabolism in Caenorhabditis elegans

1. Olga Ponomarova
2. Alyxandra N. Starbard
3. Alexandra Belfi
4. Amanda V. Anderson
5. Meera V. Sundaram
6. Albertha J.M. Walhout

Reviewed by Review Commons

PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation

1. Christopher Chin Sang
2. Gaelen Moore
3. Maria Tereshchenko
4. Michael L. Nosella
5. Hongshan Zhang
6. T. Reid Alderson
7. Morgan Dasovich
8. Anthony Leung
9. Ilya J. Finkelstein
10. Julie D. Forman-Kay
11. Hyun O. Lee

Reviewed by Review Commons

Senescent cells inhibit mouse myoblast differentiation via the SASP-lipid 15d-PGJ2 mediated modification and control of HRas

1. Swarang Sachin Pundlik
2. Alok Barik
3. Ashwin Venkateshvaran
4. Snehasudha Subhadarshini Sahoo
5. Mahapatra Anshuman Jaysingh
6. Raviswamy GH Math
7. Heera Lal
8. Maroof Athar Hashmi
9. Arvind Ramanathan

• Curated by eLife

  eLife assessment

  This manuscript outlines an interaction between senescence-related 15d-PGJ2 and the proliferation and differentiation of myoblasts, with potential implications for muscle health. This manuscript is useful in understanding the role of lipid metabolite 15d-PGJ2 in myoblast proliferation and differentiation. However, in its current form, the manuscript is incomplete as there are several concerns in the statistical analysis, lack of clarity on the mechanistic details, and concerns about the use of an immortalized C2C12 myoblasts cell line to draw major conclusions related to senescence-associated secreted phenotype.

Reviewed by eLife

Uncovering the BIN1-SH3 interactome underpinning centronuclear myopathy

1. Boglarka Zambo
2. Evelina Edelweiss
3. Bastien Morlet
4. Luc Negroni
5. Matyas Pajkos
6. Zsuzsanna Dosztanyi
7. Soren Ostergaard
8. Gilles Trave
9. Jocelyn Laporte
10. Gergo Gogl

• Curated by eLife

  eLife assessment

  This work describes a novel affinity interactomics approach that allows investigators to identify networks of protein-protein interactions in cells. The important findings presented here describe the application of this technique to the SH3 domain of the membrane remodeling Bridging Integrator 1 (BIN1), the truncation of which leads to centronuclear myopathy. The authors present solid evidence that BIN1 SH3 engages with an unexpectedly high number of cellular proteins, many of which are linked to skeletal muscle disease, and evidence is presented to suggest that BIN1 may play a role in mitosis creating the potential for new avenues in drug development efforts. Some of the findings, however, remain rather preliminary, lack sufficient replicates and may require additional experiments to definitively support the conclusions.

Reviewed by eLife

Dual-specific autophosphorylation of kinase IKK2 enables phosphorylation of substrate IκBα through a phosphoenzyme intermediate

1. Prateeka Borar
2. Tapan Biswas
3. Ankur Chaudhuri
4. Tom Huxford
5. Saikat Chakrabarti
6. Gourisankar Ghosh
7. Smarajit Polley

• Curated by eLife

  eLife assessment

  This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. These are potentially provocative results but open questions remain due to the nature of the in vitro assays and questions about protein purity and identity. Nevertheless, the findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.

Reviewed by eLife

Impact of protein and small molecule interactions on kinase conformations

1. Valentina Kugler
2. Selina Schwaighofer
3. Andreas Feichtner
4. Florian Enzler
5. Jakob Fleischmann
6. Sophie Strich
7. Sarah Schwarz
8. Rebecca Wilson
9. Philipp Tschaikner
10. Jakob Troppmair
11. Veronika Sexl
12. Pascal Meier
13. Teresa Kaserer
14. Eduard Stefan

• Curated by eLife

  eLife assessment

  This article reports an important bioluminescence-based reporter system to evaluate kinase conformations. This assay is applied to four different kinases that have unique, very special regulatory features, thereby indicating that the assay can be used to provide convincing evidence on the conformational state of a large number of kinases. This paper will be of interest to researchers working on kinases and their conformational states.

Reviewed by eLife

Toxin-based screening of C-terminal tags in Escherichia coli reveals the exceptional potency of ssrA-like degrons

1. Patrick C. Beardslee
2. Karl R. Schmitz

• Curated by eLife

  eLife assessment

  This important study employs an innovative genetic selection-based approach to identify short peptide sequences that target bacterial proteins for degradation. Using random mutagenesis they identified 5 amino acid long "degrons" that target the toxin VapC for degradation permitting survival. They provide compelling data that degrons ending in Ala-Ala are selectively recognized by the ClpXP protease and identify the sequence FKLVA as a particularly significant target. As a whole, there is enthusiasm about the author's findings, although there are also some improvements that could be made to increase the clarity and impact, mostly in the form of revisions to the text.

Reviewed by eLife

Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding

1. Ornella Bimai
2. Ipsita Banerjee
3. Inna Rozman Grinberg
4. Ping Huang
5. Lucas Hultgren
6. Simon Ekström
7. Daniel Lundin
8. Britt-Marie Sjöberg
9. Derek T Logan

• Curated by eLife

  eLife assessment

  This study advances our understanding of the allosteric regulation of anaerobic ribonucleotide reductases (RNRs) by nucleotides, providing valuable new structural insight into class III RNRs containing ATP cones. The cryo-EM structural characterization of the system is solid, but some open questions remain about the interpretation of activity/binding assays and the HDX-MS results that have been newly incorporated compared to a previous version. The work will be of interest to biochemists and structural biologists working on ribonucleotide reductases and other allosterically regulated enzymes.

Reviewed by eLife

Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling

1. Henning Mühlenbeck
2. Yuko Tsutsui
3. Mark A Lemmon
4. Kyle W Bender
5. Cyril Zipfel

• Curated by eLife

  eLife assessment

  This manuscript reports important in vitro biochemical and in planta experiments to study the receptor activation mechanism of plant membrane receptor kinase complexes with non-catalytic intracellular kinase domains. Several lines of evidence convincingly show that one such putative pseudokinase, the immune receptor EFR achieves an active conformation following phosphorylation by a co-receptor kinase, and then in turn activates the co-receptor kinase allosterically to enable it to phosphorylate down-stream signaling components. This manuscript will be of interest to scientists focusing on cell signalling and allosteric regulation.

Reviewed by eLife