Molecular Biology

A comprehensive survey of C. elegans argonaute proteins reveals organism-wide gene regulatory networks and functions

1. Uri Seroussi
2. Andrew Lugowski
3. Lina Wadi
4. Robert X Lao
5. Alexandra R Willis
6. Winnie Zhao
7. Adam E Sundby
8. Amanda G Charlesworth
9. Aaron W Reinke
10. Julie M Claycomb

• Curated by eLife

  eLife assessment

  This impressive study presents the most comprehensive analysis of the Argonautes, their small RNA partners, their targets, and their biological functions in any species to date. The work provides new insights into Argonaute-based pathways, it includes extensive validation of existing models, and describes overall a treasure-trove of reagents and datasets for future exploration of the vast Argonaute world in C. elegans.

Reviewed by eLife

Constitutive activation and oncogenicity are mediated by loss of helical structure at the cytosolic boundary of thrombopoietin receptor mutant dimers

1. Jean-Philippe Defour
2. Emilie Leroy
3. Sharmila Dass
4. Thomas Balligand
5. Gabriel Levy
6. Ian C Brett
7. Nicolas Papadopoulos
8. Céline Mouton
9. Lidvine Genet
10. Christian Pecquet
11. Judith Staerk
12. Steven O Smith
13. Stefan N Constantinescu

• Curated by eLife

  eLife assessment

  This very well-written paper advances our understanding of the mechanism of activation of the thrombopoietin receptor (TpoR), a very important cytokine receptor that regulates megakaryocyte differentiation and platelet production. The authors supply an elegant combination of NMR and cell biology experiments to support their conclusions and the data are of high quality.

Reviewed by eLife

Translation of dipeptide repeat proteins in C9ORF72 ALS/FTD through unique and redundant AUG initiation codons

1. Yoshifumi Sonobe
2. Soojin Lee
3. Gopinath Krishnan
4. Yuanzheng Gu
5. Deborah Y Kwon
6. Fen-Biao Gao
7. Raymond P Roos
8. Paschalis Kratsios

• Curated by eLife

  eLife assessment

  This valuable study by Sonobe et al uses transfected cells and patient iPSC-derived neurons to define mechanisms underlying translation of the antisense C4G2 RNA strand expressed in C9orf72-associated ALS and FTD. The authors design a series of constructs to explore the start codon required to produce toxic PR and prominent PG dipeptides in disease. Using these constructs they provide solid data that translation in the PR and PG reading frames occur due to the presence of AUG codons within the 5'UTR of the RNA strand. However, in its current form the paper is incomplete and the conclusions require additional experimental support.

Reviewed by eLife

Phosphorylation of Rab29 at Ser185 regulates its localization and role in the lysosomal stress response in concert with LRRK2

1. Tadayuki Komori
2. Tomoki Kuwahara
3. Tetta Fujimoto
4. Maria Sakurai
5. Ikuko Koyama-Honda
6. Mitsunori Fukuda
7. Takeshi Iwatsubo

Reviewed by Review Commons

STAT3 promotes RNA polymerase III-directed transcription by controlling the miR-106a-5p/TP73 axis

1. Cheng Zhang
2. Shasha Zhao
3. Huan Deng
4. Shihua Zhang
5. Juan Wang
6. Xiaoye Song
7. Deen Yu
8. Yue Zhang
9. Wensheng Deng

• Curated by eLife

  eLife assessment

  The author arrive at the convincing conclusion that STAT3 expression promotes TFIIIB assembly through miR-106A-5p-mediated inhibition of TP73 expression, thereby increasing Pol III transcription, which contributes to enhanced cell proliferation. The data are very good and clearly support the proposed model.

Reviewed by eLife

Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle

1. Nurul Jannah Mohamed Nasir
2. Hans Heemskerk
3. Julia Jenkins
4. Nur Hidayah Hamadee
5. Ralph Bunte
6. Lisa Tucker-Kellogg

Reviewed by Review Commons

eCRUIS captures RNA-protein interaction in vitro and in vivo

1. Ziheng Zhang
2. Yuanbing Zhang
3. Ji-Long Liu

Reviewed by Arcadia Science

Recognition of galactose by a scaffold protein recruits a transcriptional activator for the GAL regulon induction in Candida albicans

1. Xun Sun
2. Jing Yu
3. Cheng Zhu
4. Xinreng Mo
5. Qiangqiang Sun
6. Dandan Yang
7. Chang Su
8. Yang Lu

• Curated by eLife

  eLife assessment

  This important manuscript investigates the circuitry connecting the galactose utilization regulon of the human pathogen and model organism Candida albicans to the sensing of galactose. In the non-pathogenic model yeast Saccharomyces cerevisiae this circuit represents a textbook model that rivals the lac operon as a teaching tool. Using a broad array of mainly classical approaches, this study convincingly demonstrates the transcriptional activators that are required for galactose (and GlcNAc) responsive galactose metabolic genes in C. albicans. The recognition of just how different the regulation of the galactose pathway across fungal species represents an important advance in our understanding of the evolution of the regulatory control of these circuits, and would make a nice addition to the textbook version of eukaryotic gene regulation.

Reviewed by eLife

Hypoxia truncates and constitutively activates the key cholesterol synthesis enzyme squalene monooxygenase

1. Hudson W Coates
2. Isabelle M Capell-Hattam
3. Ellen M Olzomer
4. Ximing Du
5. Rhonda Farrell
6. Hongyuan Yang
7. Frances L Byrne
8. Andrew J Brown

• Curated by eLife

  eLife assessment

  Hudson and colleagues provide a new link between oxygen sensing and cholesterol synthesis. In previous studies, this group had shown that the cholesterol synthetic enzyme squalene monooxygenase (SM) is subjected to partial proteasomal degradation, which leads to the production of a truncated, constitutively active enzyme. Here, the authors provide evidence for the physiological significance of SM truncation by showing that subjecting cells to hypoxia (oxygen deprivation) induces truncation of SM. The synthesis of cholesterol requires 11 molecules of oxygen and SM is the first oxygen-dependent enzyme in the cholesterol-committed branch of the pathway. It is possible that constitutive activation of SM under oxygen-deficient conditions could reduce the toxicity of squalene and other sterol intermediates.

Reviewed by eLife

The role of Limch1 alternative splicing in skeletal muscle function

1. Matthew S. Penna
2. George G. Rodney
3. Rong-Chi Hu
4. Thomas A. Cooper

Reviewed by Review Commons