Molecular Biology

Ribosomal RNA methylation by GidB modulates discrimination of mischarged tRNA

1. Zhuo Bi
2. Yu-Xiang Chen
3. Iris D Young
4. Mohamad T Dandan
5. Hemant Joshi
6. Hong-Wei Su
7. Yuemeng Chen
8. Jia-Yao Hong
9. James S Fraser
10. Babak Javid

• Curated by eLife

  eLife Assessment

  This important study by Bi and colleagues employed a clever genetics screen to uncover the role of the GidB rRNA methylase in translation fidelity, under certain conditions, in Mycobacterium smegmatis. The findings are solid, supporting the findings that the loss of GidB results in mistranslation. The work contributes to a more in-depth understanding of mycobacterial translation fidelity and will be of interest to microbiologists.

Reviewed by eLife

Impacts of DNA methylation on H2A.Z deposition and nucleosome stability

1. Rochelle M Shih
2. Yasuhiro Arimura
3. Hide A Konishi
4. Hironori Funabiki

• Curated by eLife

  eLife Assessment

  This study provides valuable mechanistic insight into the mutually exclusive distributions of the histone variant H2A.Z and DNA methylation by testing two hypotheses: (i) that DNA methylation suppresses H2A.Z deposition by ATP-dependent chromatin remodelling complexes, and (ii) that DNA methylation destabilizes H2A.Z nucleosomes, thereby preventing H2A.Z retention. Through a series of well-designed and carefully executed experiments, solid support is presented for the first hypothesis. The evidence supporting the second hypothesis is less complete, and the extent to which either mechanism is responsible for H2A.Z exclusion from methylated DNA remains not entirely clear. This work will be of broad interest to researchers in chromatin biology and epigenetics.

Reviewed by eLife

Decoupling AMPK from fatty acid synthesis allows maintenance of fitness late in life

1. Hanane Hadj-Moussa
2. Megan Ulusan
3. Dorottya Horkai
4. Mohammed Kamran Afzal Mirza
5. Jonathan Houseley

• Curated by eLife

  eLife Assessment

  This study addresses an important question in aging biology by combining metabolic, genetic, and functional approaches to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast. The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in shaping distinct aging-associated phenotypes is convincing overall, with the engineered A2A strain providing a particularly elegant demonstration of coordinated metabolic regulation. However, several conclusions would benefit from clarification or moderation, particularly regarding the relationship between late-life fitness and replicative lifespan, the interpretation of "senescence," the proposed existence of distinct aging subpopulations, and the extent to which the data support mechanistic claims about lipid starvation, acetyl-CoA excess, and chromatin-based aging pathways.

Reviewed by eLife

Nucleolar dynamics are determined by the ordered assembly of the ribosome

1. Jessica Sheu-Gruttadauria
2. Xiaowei Yan
3. Nico Stuurman
4. Riley O Ogrean
5. Sabrina Lin
6. Stephen N. Floor
7. Ronald D. Vale

Reviewed by Review Commons

Uncoupling the TFIIH Core and Kinase Modules Leads To Misregulated RNA Polymerase II CTD Serine 5 Phosphorylation

1. Gabriela Giordano
2. Robin Buratowski
3. Célia Jeronimo
4. Christian Poitras
5. François Robert
6. Stephen Buratowski

• Curated by eLife

  eLife Assessment

  This important work demonstrates the role of physically linking the core and CTD kinase modules of TFIIH via separate domains of subunit Tfb3 in confining RNA Polymerase II Serine 5 CTD phosphorylation to promoter regions of transcribed genes in budding yeast. The main findings, resulting from analyses of viable Tfb3 mutants in which the linkage between TFIIH core and kinase modules has been severed, are supported by solid evidence from in vitro and in vivo experiments. The new findings raise the intriguing possibility that the Tfb3-mediated connection between core and kinase modules of TFIIH is an evolutionary addition to an ancestral state of physically unconnected enzymes.

Reviewed by eLife

Single-domain antibody inhibitors target the coiled coil arms of the Bacillus subtilis SMC complex

1. Ophélie J Gosselin
2. Michael Taschner
3. Lea M Huber-Hürlimann
4. Markus A Seeger
5. Stephan Gruber

• Curated by eLife

  eLife Assessment

  This important study introduces an innovative synthetic nanobody approach to probe the function of the bacterial SMC complex. The work is a compelling example of the potential of this approach. The authors generate protein chimeras to provide convincing evidence that their identified nanobodies target the coiled-coil region of the SMC subunit, demonstrating that this region is critical for SMC function in vivo. Overall, the work is significant for the fields of genome organisation, SMC protein biology, synthetic biology, and bacterial cell biology.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

In extracto cryo-EM reveals eEF2 as a major hibernation factor on 60S and 80S particles

1. Zahra Seraj
2. Ximena Zottig
3. Chun-Ying Huang
4. Anna B Loveland
5. Stephen Diggs
6. Emily Sholi
7. Nikolaus Grigorieff
8. Andrei A Korostelev

• Curated by eLife

  eLife Assessment

  In this important work, it is demonstrated that certain high-resolution cryo-EM structures can be obtained by using concentrated cell extracts without purification. The compelling results with the mammalian ribosomes demonstrate the utility of this approach for this molecule and complexes with elongation factor 2. Moreover, this work also demonstrates the utility of 2D template matching for particle picking for structure determination by single-particle averaging pipelines.

Reviewed by eLife

Ubiquitin ligase ITCH regulates life cycle of SARS-CoV-2 virus

1. Qiwang Xiang
2. Camille Wouters
3. Peixi Chang
4. Yu-Ning Lu
5. Mingming Liu
6. Haocheng Wang
7. Haley Heine
8. Sunning Qian
9. Junqin Yang
10. Andrew Pekosz
11. Yanjin Zhang
12. Jiou Wang

• Curated by eLife

  eLife Assessment

  This valuable study demonstrates that the E3 ligase ITCH regulates several steps of the SARS-CoV-2 replication cycle by enhancing ubiquitination of viral envelope and membrane proteins. The phenotypic data are based on solid evidence showing a role for ITCH in distinct phases of viral replication and host processes. The findings lay the ground work for future studies to decipher detailed molecular mechanisms that explain how ITCH regulates SARS-CoV-2.

Reviewed by eLife

Mechanistic insights into transcriptional regulation of ARHGAP36 expression identify a factor predictive of neuroblastoma survival

1. Serhiy Havrylov
2. Armin M Gamper
3. Ordan J Lehmann

• Curated by eLife

  eLife Assessment

  This important study examines the potential role of ARHGAP36 transcriptional regulation by FOXC1 in controlling sonic hedgehog signaling in human neuroblastoma. While there are many solid findings that strongly support this signaling pathway, there are some aspects of the study that are underdeveloped, particularly the generalizability in the context of cancer cells.

Reviewed by eLife

Highly frequent undesired insertional mutagenesis during Drosophila genome editing

1. Emma Källstig
2. Evelyne Ruchti
3. Medha Raman
4. Jamshid Asadzadeh
5. Bernard L. Schneider
6. Brian D. McCabe

Reviewed by Review Commons