Genetics

Bidirectional promoter activity from expression cassettes can drive off-target repression of neighboring gene translation

1. Emily Nicole Powers
2. Charlene Chan
3. Ella Doron-Mandel
4. Lidia Llacsahuanga Allcca
5. Jenny Kim Kim
6. Marko Jovanovic
7. Gloria Ann Brar

• Curated by eLife

  eLife assessment

  Powers and colleagues reveal that commonly used "genetic markers" (selectable cassettes that allow for genome modification) may lead to unintended consequences and unanticipated phenotypes. These consequences arise from cryptic expression directed from within the cassettes into adjacent genomic regions. In this work, they identify a particularly strong example of marker interference with a neighboring gene's expression and develop and test next-generation tools that circumvent the problem. The work will be primarily of interest to yeast biologists using these types of tools and interpreting these types of data.

Reviewed by eLife

Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification

1. Zhanying Feng
2. Zhana Duren
3. Jingxue Xin
4. Qiuyue Yuan
5. Yaoxi He
6. Bing Su
7. Wing Hung Wong
8. Yong Wang

• Curated by eLife

  eLife assessment

  This manuscript is of interest to scientists studying the genetics of complex human diseases. The approach introduced here is potentially useful for the identification of tissues linked to complex disease heritability. Currently, the key claims of the paper are not entirely supported by the data. The claims may become well supported once the authors improve statistical rigor and perform a more comprehensive comparison with other methods.

Reviewed by eLife

Magnesium and the magnesium transporter UEX regulate sleep via Ca ²⁺ -dependent CREB signaling and a CNK-ERK pathway

1. Xin Yuan
2. Huimei Zheng
3. Xiao Xu
4. Huan Deng
5. Xiaohang Yang
6. Yongmei Xi

• Curated by eLife

  eLife assessment

  This manuscript provides valuable evidence for the role of magnesium homeostasis and relevant signaling pathway in Drosophila sleep regulation. It will be of interest to cellular biologists and neuroscientists interested in sleep:wake behavior and the potential role of magnesium in promoting sleep. Nevertheless, the evidence for the key claims of the manuscript is incomplete and is not fully supported by the data as reasonable alternative explanations exist.

Reviewed by eLife

Interdependent progression of bidirectional sister replisomes in E. coli

1. Po Jui Chen
2. Anna B McMullin
3. Bryan J Visser
4. Qian Mei
5. Susan M Rosenberg
6. David Bates

• Curated by eLife

  eLife assessment

  This paper reports a fundamental set of new results describing replisome organization and dynamics in E. coli. Cellular sites of active DNA replication (forks) spatially co-localize into structures termed replication factories, but the biological rationale for this fork co-localization has remained unknown. In an elegant study, the authors provide strong evidence that these factories are necessary to both coordinate and promote the progression of colocalized forks, and to help prevent them from spontaneously and prematurely dissociating. Through these findings, it is shown, for the first time, that replisomes' association has a beneficial impact on the bacterium. This is important work that provides robust data in favor of the factory and splitting model.

Reviewed by eLife

Deregulations of miR‐1 and its target Multiplexin promote dilated cardiomyopathy associated with myotonic dystrophy type 1

1. Anissa Souidi
2. Masayuki Nakamori
3. Monika Zmojdzian
4. Teresa Jagla
5. Yoan Renaud
6. Krzysztof Jagla

Reviewed by Review Commons

A novel overlapping gene azyx-1 affects the translation of zyxin in C. elegans

1. Bhavesh S. Parmar
2. Ellen Geens
3. Elke Vandewyer
4. Amanda Kieswetter
5. Christina Ludwig
6. Liesbet Temmerman

Reviewed by Review Commons

Exploiting the mediating role of the metabolome to unravel transcript-to-phenotype associations

1. Chiara Auwerx
2. Marie C Sadler
3. Tristan Woh
4. Alexandre Reymond
5. Zoltán Kutalik
6. Eleonora Porcu

• Curated by eLife

  eLife assessment

  Auwerx and colleagues take a new approach to mine large datasets of the intermediary molecular data between GWAS and phenotype, touncover molecular mechanisms that lead from a GWAS hit to a phenotypic effect. The approach should be of great use to all (human) geneticists. Revisions are necessary to ensure that the significant findings from this approach are understood by the bioinformatic community and that these methods can be applied generally, given that the paper's main novelty is in its approach to mine large datasets, rather than a specific, key molecular finding.

Reviewed by eLife

Relating pathogenic loss-of-function mutations in humans to their evolutionary fitness costs

1. Ipsita Agarwal
2. Zachary L Fuller
3. Simon R Myers
4. Molly Przeworski

• Curated by eLife

  eLife assessment

  This paper directly estimates the fitness cost of loss-of-function mutations in almost every gene in the human genome, providing an interpretable measure of the severity of mutations. The authors then compare datasets of presumably healthy individuals and individuals affected by severe complex disorders or genetic disorders, finding enrichment of de novo loss-of-function mutations in highly constrained genes among probands alongside other illuminating results. This important study will be useful to researchers interested in interpreting and prioritizing disease-causing mutations and in the process of human evolution. Overall, the approach is elegant and the results are of high quality and compelling.

Reviewed by eLife

Single-cell RNA sequencing identifies regulators of differentiation and nutritional cues in Drosophila female germ cells

1. Zhipeng Sun
2. Todd G. Nystul
3. Guohua Zhong

Reviewed by Review Commons

Methylglyoxal-derived hydroimidazolone, MG-H1, increases food intake by altering tyramine signaling via the GATA transcription factor ELT-3 in Caenorhabditis elegans

1. Muniesh Muthaiyan Shanmugam
2. Jyotiska Chaudhuri
3. Durai Sellegounder
4. Amit Kumar Sahu
5. Sanjib Guha
6. Manish Chamoli
7. Brian Hodge
8. Neelanjan Bose
9. Charis Amber
10. Dominique O Farrera
11. Gordon Lithgow
12. Richmond Sarpong
13. James J Galligan
14. Pankaj Kapahi

• Curated by eLife

  eLife assessment

  The work, which examines how Advanced Glycation End-products (AGEs), commonly found in processed and other cooked foods, affect eating behavior and signaling in the nematode C. elegans, is in a fundamentally important area of research with clear translational potential for humans. Some aspects of the manuscript are compelling, including the well-characterized assays on food intake, while other aspects are still incomplete, such as the mechanistic work on the neural network responsible for the response to AGEs.

Reviewed by eLife