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Current Issue of Trends in Genetics


Issue: Trends in Genetics
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Trends in Genetics
This journal offers authors two options (open access or subscription) to publish research

Aug 01, 2022

Volume 38Issue 8p785-884, e1-e2
While loss-of-function mutations in some genes do not produce overt phenotypes, inactivation of other so called essential genes is lethal. Detailed studies of biological roles of essential genes greatly benefit from the ability to turn them off at will. Recent advances in genome editing methodologies have enabled several laboratories to demonstrate the feasibility of conditional mutagenesis in zebrafish. On pages 856–868 of this issue, Kalvaitytė and Balciunas discuss different ways of inducing conditional loss of function in zebrafish, as well as means of engineering such mutants. Illustration on the cover depicts the possibility of conditionally inactivating genes in adult zebrafish. Cover art: Miglė Kalvaitytė and Vita Tomkutė....
While loss-of-function mutations in some genes do not produce overt phenotypes, inactivation of other so called essential genes is lethal. Detailed studies of biological roles of essential genes greatly benefit from the ability to turn them off at will. Recent advances in genome editing methodologies have enabled several laboratories to demonstrate the feasibility of conditional mutagenesis in zebrafish. On pages 856–868 of this issue, Kalvaitytė and Balciunas discuss different ways of inducing conditional loss of function in zebrafish, as well as means of engineering such mutants. Illustration on the cover depicts the possibility of conditionally inactivating genes in adult zebrafish. Cover art: Miglė Kalvaitytė and Vita Tomkutė.

Spotlights

  • Retooling conditional gene expression using a floxed exon

    • Mary B. Kroetz
    The Cre-lox system is a powerful approach for the spatiotemporal regulation of gene expression. Shaffer and Greenwald recently devised an adaptation of this system in which a floxed artificial exon promotes premature termination of translation and nonsense-mediated decay of mRNA, allowing for robust conditional regulation of transgenes and endogenous loci.
  • Catastrophic DNA replication in unscheduled tetraploid cells

    • Gwenola Manic,
    • Lorenzo Galluzzi,
    • Ilio Vitale
    Unscheduled tetraploidy is a metastable state that rapidly evolves into aneuploidy. Recent findings reported by Gemble et al. demonstrate that freshly formed tetraploid cells fail to accumulate the required amounts of DNA replication factors during the first G1 phase after whole-genome duplication (WGD), culminating in genetic instability in the subsequent S phase and extensive karyotypic alterations.

Forum

  • Intron retention: importance, challenges, and opportunities

    • Justin J.-L. Wong,
    • Ulf Schmitz
    Recent landmark discoveries have underpinned the physiological importance of intron retention (IR) across multiple domains of life and revealed an unexpected breath of functions in a large variety of biological processes. Despite significant progress in the field, some challenges remain. Once solved, opportunities will arise for discovering more functions of IR.
  • Structure-specific nucleases: role in Okazaki fragment maturation

    • Lingzi Ma,
    • Haitao Sun,
    • Tharindumala Abeywardana,
    • Li Zheng,
    • Binghui Shen
    Proper function of structure-specific nucleases is key for faithful Okazaki fragment maturation (OFM) process completion. Deregulation of such nucleases leads to aberrant OFM and causes a spectrum of mutations, some of which may confer survival outcomes under specific stresses and serve as attractive targets for therapeutic intervention in human cancers.
  • mRNA-binding proteins and cell cycle progression

    • Michael Polymenis
    Proteins that bind to each mRNA may affect the latter’s abundance and location in the cell and how well ribosomes will translate that mRNA into a protein. Hence, mRNA-binding proteins (mRBPs) represent obvious control points in gene expression. Surprisingly, little is known about mRBPs and cell-cycle progression.
  • The versatile relationships between eIF4E and eIF4E-interacting proteins

    • Greco Hernández
    RNA metabolism and gene expression lie at the core of cellular life. eIF4E has emerged as a central interface in both processes as it plays critical roles in mRNA processing, transport, translation, and storage. Crucially, eIF4E depends on its association with a universe of proteins to form biologically meaningful complexes.

Opinions

Series: Revisiting discoveries that transformed genetics

  • A decade of molecular cell atlases

    • Stephen R. Quake
    Open Access
    In recent years there has been tremendous progress towards deep molecular characterization of cell types using single-cell transcriptome sequencing, creating so-called ‘cell atlases’. These atlases provide a basic understanding of how different cell types of the same organism – which all share the genome – make distinct use of subsets of genes from the genome to create a variety of distinct cell types across tissues with specialized functions. In this opinion article I discuss some of the history and technological innovations that led to the development of whole-organism atlases.
  • Earth Biogenome Project: present status and future plans

    • Pushpendra Kumar Gupta
    Earth Biogenome Project (EBP) is an ambitious project targeted to provide high-quality reference genome sequences for all 1.8 million named extant (living) eukaryote species. The project was launched on 1 November 2018 with an initial 2 years’ pilot phase (2018–2020) followed by Phase I (2020–2023), during which genomes of 9400 species will be sequenced. The genomes of the remaining ~1.7 million species will be sequenced in a planned manner during Phase II (2024–2027) and Phase III (2028–2030). In view of the excitement generated and the progress already made, the subject was covered in a Special Feature of a recent issue of PNAS (25 January 2022).

Reviews

  • ADAR1 and its implications in cancer development and treatment

    • Allison R. Baker,
    • Frank J. Slack
    The family of adenosine deaminases acting on RNA (ADARs) regulates global gene expression output by catalyzing adenosine-to-inosine (A-to-I) editing of double-stranded RNA (dsRNA) and through interacting with RNA and other proteins. ADARs play important roles in development and disease, including an increasing connection to cancer progression. ADAR1 has demonstrated a largely pro-oncogenic role in a growing list of cancer types, and its function in cancer has been attributed to diverse mechanisms.
  • Into the multiverse: advances in single-cell multiomic profiling

    • Silvia Ogbeide,
    • Francesca Giannese,
    • Laura Mincarelli,
    • Iain C. Macaulay
    Open Access
    Single-cell transcriptomic approaches have revolutionised the study of complex biological systems, with the routine measurement of gene expression in thousands of cells enabling construction of whole-organism cell atlases. However, the transcriptome is just one layer amongst many that coordinate to define cell type and state and, ultimately, function. In parallel with the widespread uptake of single-cell RNA-seq (scRNA-seq), there has been a rapid emergence of methods that enable multiomic profiling of individual cells, enabling parallel measurement of intercellular heterogeneity in the genome, epigenome, transcriptome, and proteomes.
  • The evolution of gene regulation on sex chromosomes

    • Daniel E. Shaw,
    • Michael A. White
    Sex chromosomes have evolved repeatedly across the tree of life. Most work has focused on the loss of coding regions from sex-limited chromosomes through the accumulation of deleterious mutations. By comparison, less is known about how the regulatory landscape evolves. We review theories of how regulatory landscapes evolve on sex chromosomes and the overall impact they have on gametolog expression. We integrate empirical studies on sex chromosomes with theoretical work to synthesize how regulatory evolution could occur on sex chromosomes.
  • Featured Article
  • Conditional mutagenesis strategies in zebrafish

    • Miglė Kalvaitytė,
    • Darius Balciunas
    Gene disruption or knockout is an essential tool for elucidating gene function. Conditional knockout methodology was developed to further advance these studies by enabling gene disruption at a predefined time and/or in discrete cells. While the conditional knockout method is widely used in the mouse, technical limitations have stifled direct adoption of this methodology in other animal models including the zebrafish. Recent advances in genome editing have enabled engineering of distinct classes of conditional mutants in zebrafish.
  • Featured Article
  • Mitochondrial genome engineering coming-of-age

    • Jose Domingo Barrera-Paez,
    • Carlos T. Moraes
    The mitochondrial genome has been difficult to manipulate because it is shielded by the organelle double membranes, preventing efficient nucleic acid entry. Moreover, mitochondrial DNA (mtDNA) recombination is not a robust system in most species. This limitation has forced investigators to rely on naturally occurring alterations to study both mitochondrial function and pathobiology. Because most pathogenic mtDNA mutations are heteroplasmic, the development of specific nucleases has allowed us to selectively eliminate mutant species.

Genome of the Month

  • The kākāpō (Strigops habroptilus)

    • Nicolas Dussex,
    • Bruce C. Robertson,
    • Love Dalén,
    • Erich D. Jarvis
    Open Access
    The kākāpō, Strigops habroptilus, is a flightless and critically endangered parrot from New Zealand. The species belongs to a unique lineage of parrots, endemic to the archipelago that diverged from other parrots ~82 million years ago (mya), as New Zealand split from Gondwana. The kākāpō genome represents one of the first high-quality chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP) and is an important resource for future studies on evolution and conservation.

Correction

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