Molecular Biology

Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules

1. Yuzuru Itoh
2. Vivek Singh
3. Anas Khawaja
4. Andreas Naschberger
5. Minh Duc Nguyen
6. Joanna Rorbach
7. Alexey Amunts

• Curated by eLife

  Evaluation Summary:

  As a consequence of the bacterial origin of mitochondria, a range of medically relevant antimicrobials can affect not only bacteria but also human cells. For example, they may inhibit mitochondrial protein synthesis, giving rise to important side-effects during medical treatment, such as hearing loss or renal toxicity in patients treated with aminoglycosides. In this manuscript, the authors present the structure of the human mitochondrial small ribosomal subunit bound to one such antibiotics, streptomycin. This cryoEM-based structural analysis will be of interest to scientists in the infectious disease community as well as those interested in ribosome structural biology. It provides an important advance that could aid future medicinal chemistry efforts to improve the therapeutic potential of streptomycin derivatives.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

1. Minato Hirano
2. Gaddiel Galarza-Muñoz
3. Chloe Nagasawa
4. Geraldine Schott
5. Liuyang Wang
6. Alejandro L Antonia
7. Vaibhav Jain
8. Xiaoying Yu
9. Steven G Widen
10. Farren BS Briggs
11. Simon G Gregory
12. Dennis C Ko
13. William S Fagg
14. Shelton Bradrick
15. Mariano A Garcia-Blanco

• Curated by eLife

  Evaluation Summary:

  In this study, DDX39B, a factor with known functions in mRNA splicing and nuclear export, is shown to regulate Foxp3, a lineage marker for T-regulatory cells in the immune system. The interactions are positioned in the context of multiple sclerosis and autoimmune inflammatory condition. The work would be of interest to immunologists and those studying RNA-mediated regulation and cellular signaling.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Topologically engineered antibodies and Fc-fusion proteins: a new class of multifunctional therapeutic candidates for SARS-CoV-2, cancer, and other disease

1. Daniel J. Capon
2. Larisa Troitskaya
3. Nelson Lap Shun Chan
4. Marina Fomin
5. Ursula Edman
6. Brendon Frank
7. Jing Jin
8. Rachel Martinelli
9. Benjamin Z. Capon
10. Ginger A. Ferguson
11. Malcolm L. Gefter
12. Graham Simmons

Reviewed by ScreenIT

Concerted modification of nucleotides at functional centers of the ribosome revealed by single-molecule RNA modification profiling

1. Andrew D Bailey
2. Jason Talkish
3. Hongxu Ding
4. Haller Igel
5. Alejandra Duran
6. Shreya Mantripragada
7. Benedict Paten
8. Manuel Ares

• Curated by eLife

  Evaluation Summary:

  In this manuscript Bailey et al use single molecule RNA sequencing to dissect the functional relationships between distinct rRNA modification sites. Their method allows for the deconvolution of distinct subpopulations of rRNA and provides new insights in the installment of rRNA modifications, ribosome heterogeneity and ribosome biogenesis. The paper presents a major technological advance in mapping nucleoside modifications across single RNA molecules and identifying factors that influence these modifications.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Inositol polyphosphate multikinase physically binds to the SWI/SNF complex and modulates BRG1 occupancy in mouse embryonic stem cells

1. Jiyoon Beon
2. Sungwook Han
3. Hyeokjun Yang
4. Seung Eun Park
5. Kwangbeom Hyun
6. Song-Yi Lee
7. Hyun-Woo Rhee
8. Jeong Kon Seo
9. Jaehoon Kim
10. Seyun Kim
11. Daeyoup Lee

• Curated by eLife

  Evaluation Summary:

  This study describes a physical interaction between the Inositol polyphosphate multikinase enzyme (IPMK) and the SWI/SNF chromatin-remodeling complex. IMPK modulates SWI/SNF chromatin binding in particular at the transcription start sites of promoters with bivalent chromatin modifications in embryonic stem cells to regulate gene expression. This study will be of general interest to the epigenetics and gene expression communities.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

An efficient and robust laboratory workflow and tetrapod database for larger scale environmental DNA studies

1. Jan Axtner
2. Alex Crampton-Platt
3. Lisa A Hörig
4. Azlan Mohamed
5. Charles C Y Xu
6. Douglas W Yu
7. Andreas Wilting

Reviewed by GigaScience

Macrophage inflammation resolution requires CPEB4-directed offsetting of mRNA degradation

1. Clara Suñer
2. Annarita Sibilio
3. Judit Martín
4. Chiara Lara Castellazzi
5. Oscar Reina
6. Ivan Dotu
7. Adrià Caballé
8. Elisa Rivas
9. Vittorio Calderone
10. Juana Díez
11. Angel R Nebreda
12. Raúl Méndez

• Curated by eLife

  Evaluation Summary:

  This study examined the role of CEBP4 in resolution of immune inflammatory responses. The manuscript uses genetic and pharmacologic approaches to demonstrate requirement of CEBP4 for survival following LPS administration and outlines certain downstream details of the mechanism. However, certain conclusions pertaining to this mechanism are either weak or not fully clarified. Further, the study proposes that RNA-binding proteins CPEB4 and TTP play important roles in regulating inflammation-associated mRNA transcripts by binding to CPEs or AREs to promote RNA stability or degradation. There is general agreement that most of the claims in the paper appear reasonably well-supported by the experimental data. However, there are some concerns regarding the robustness and significance of the presented data and conclusions as indicated in the individual reviews that require revision.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors).

Reviewed by eLife

Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid

1. Preeti Dhaka
2. Ankur Singh
3. Shweta Choudhary
4. Rama Krishna Peddinti
5. Pravindra Kumar
6. Gaurav Kumar Sharma
7. Shailly Tomar

Reviewed by ScreenIT

Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells

1. Kei Fukuda
2. Yoshinori Makino
3. Satoru Kaneko
4. Chikako Shimura
5. Yuki Okada
6. Kenji Ichiyanagi
7. Yoichi Shinkai

• Curated by eLife

  Evaluation Summary:

  The majority, but not all retrotransposons undergo massive reprogramming of their methylation states during germ cell development. This manuscript tests the contribution of binding motifs for KRAB-Zinc Finger Proteins (KZFPs) and the position of retrotransposons relative to genes to explain the variable methylation dynamics of different retrotransposon families, namely L1, SVA and LTR12, as well as potential inter-individual variation during male germ cell development in humans, using an integrative analyses of available sequencing datasets. By bringing insights into the complex regulation of retrotransposons, this study could be of particular interest to the epigenetics community. Some additional analyses would strengthen the inferences made.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Intragenomic rearrangements in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses

1. Roberto Patarca
2. William A. Haseltine

Reviewed by ScreenIT