Molecular Biology

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 metabolomics, transcriptomics, molecular genetics, and functional analyses 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 preserving fitness during aging is convincing overall, and the engineered A2A strain provides an elegant demonstration that coordinated modulation of distinct acetyl-CoA metabolic branches can increase the proportion of aged cells with a low-senescence phenotype. The study provides significant insight into mechanisms that allow aging cells to maintain fitness without extending replicative lifespan.

Reviewed by eLife

Site-Specific Inhibition of Translation Initiation via 2’-O-methylation

1. Adam Suh
2. Stephanie Mou
3. Emmely A. Patrasso
4. Hannah Serio
5. Kevin Vasquez
6. Rui Wang
7. Smriti Sangwan
8. Yang Yi
9. Daniel Arango

Reviewed by preLights

Ligand-dependent enhancer activation indirectly modulates non-target promoters in a chromatin domain

1. Darshika Bohra
2. Zubairul Islam
3. Sundarraj Nidharshan
4. Aprotim Mazumder
5. Dimple Notani

• Curated by eLife

  eLife Assessment

  The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. Their results, which are supported by solid evidence and will be important for the field, suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, through an indirect mechanism as the estrogen responsive enhancer does not loop with the TFF3 promoter. The mechanism of activation may involve condensate formation, however, more future work is needed to fully support a condensate based model. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

Reviewed by eLife

Stochastic splicing and deterministic inclusion of variable exons promote diversification of Down Syndrome Cell Adhesion Molecule expression

1. Anna Lassota
2. Thomas C. Dix
3. Deepanshu N. D. Singh
4. Matthias Soller

Reviewed by Review Commons

A systematic interactome of SET1C expands its functional landscape and identifies candidate regulatory connections

1. Pierre Luciano
2. Kihyun Park
3. Stéphane Audebert
4. Luc Camoin
5. Carlos A Niño
6. Da Kyeong Park
7. Isabella E Maudlin
8. Marion Dubarry
9. Lara Lee
10. Marlene Oeffinger
11. Jean D Beggs
12. Young Hye Kim
13. Jaehoon Kim
14. Bernhard Dichtl
15. Vincent Géli

• Curated by eLife

  eLife Assessment

  This study uses the yeast two-hybrid assay to identify proteins that may interact with yeast Set1 and other subunits of COMPASS/Set1C, the histone H3K4 methyltransferase, providing also some evidence for Set1 sumoylation and a role of SET1C methylating other factors in vitro. The results are valuable and they should contribute to understanding the functions of the conserved SET1C complex, as they suggest potential functional connections with RNA biogenesis, chromatin remodeling, and non-histone methylation whose implications would yet need to be explored. Nevertheless, apart from the fact that only a small subset of the Y2H interactions is further examined, the validating experiments are only partial or inconclusive, the strength of evidence being incomplete at this point, although with improvements over the previous version.

Reviewed by eLife

Optimised genome editing for precise DNA insertion and substitution using prime editors in zebrafish

1. Yosuke Ono
2. Martin Peterka
3. Michael Love
4. Amir Khan
5. Felix Bowers
6. Ashish Bhandari
7. Euan Gordon
8. Jonathan S Ball
9. Chrissy Hammond
10. Charles R Tyler
11. Steve Rees
12. Mohammad Bohlooly-Y
13. Marcello Maresca
14. Steffen Scholpp

• Curated by eLife

  eLife Assessment

  This study presents a comparison of the efficiency and precision of two prime editing methods to introduce single-nucleotide variants and longer exogenous DNA sequences into the zebrafish genome. Convincing data support the conclusion that the PE2 prime editor Nickase is more effective at introducing single-nucleotide variants, while the PEn prime editor nuclease is more effective at integrating sequences from 3 up to 46 base pairs, for both somatic and germline editing. The results will be valuable for the zebrafish community, in particular to model human disease variants in this model organism.

Reviewed by eLife

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

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