Trends in Genetics最新文献

Cancer continues to be a major global health challenge, accounting for 10 million deaths annually worldwide. Since the inception of genome-wide cancer sequencing studies 20 years ago, a core set of ~700 oncogenes and tumor suppressor genes has become the basis for cancer research. However, this research has been based largely on an understanding that the human genome encodes ~19 500 protein-coding genes. Complementing this genomic landscape, recent advances have described numerous microproteins which are now poised to redefine our understanding of oncogenic processes and open new avenues for therapeutic intervention. This review explores the emerging evidence for microprotein involvement in cancer mechanisms and discusses potential therapeutic applications, with an emphasis on highlighting recent advances in the field.

Hundreds of thousands of arthropod species use silk to capture prey, build protective structures, or anchor eggs. While most silk-producers are terrestrial, caddisflies construct silken capture nets and portable cases in aquatic environments. Given the potential practical applications of this underwater bioadhesive, there is an emerging body of research focused on understanding the evolution of the genetic architecture of aquatic silk. This research has unveiled molecular adaptations specific to caddisfly silk, such as extensive phosphorylation of the primary silk protein and the existence of numerous unique accessory silk proteins. We discuss the molecular evolution of caddisfly silk genes, how they interact with the environment, and suggest future directions for caddisfly silk genetics research.

SNF2-family DNA translocases, a large family of ATPases, have poorly defined roles in genomic stability. In a recent study, Feng et al. identified a synthetic lethal interaction between the SNF2 translocase SMARCAL1 and Fanconi anemia (FA) group M (FANCM), revealing a new genetic buffering mechanism that maintains genome stability by aiding DNA replication at loci enriched in simple repeats.

Thanks to twin studies, it has been known for decades that human same-sex sexual behavior (SSB) has a substantial heritable component. However, only recently have large genome-wide association studies (GWAS) begun to illuminate the complex genetics involved. These studies have established that SSB is influenced by many common genetic variants, each with tiny but cumulative effects. The evolutionary explanation for the persistence of genetic variants associated with SSB, despite their apparent fitness costs, remains uncertain. In this review, we synthesize advances in understanding the genetic and evolutionary bases of SSB, while identifying the many areas in which we still have much to learn.

Neuronal activity, including sensory-evoked and spontaneous firing, regulates the expression of a subset of genes known as activity-dependent genes. A key issue in this process is the activation and accumulation of transcription factors (TFs), which bind to cis-elements at specific enhancers and promoters, ultimately driving RNA synthesis through transcription machinery. Epigenetic factors such as histone modifiers also play a crucial role in facilitating the specific binding of TFs. Recent evidence from epigenome analyses and imaging studies have revealed intriguing mechanisms: the default chromatin structure at activity-dependent genes is formed independently of neuronal activity, while neuronal activity modulates spatiotemporal dynamics of TFs and their interactions with epigenetic factors (EFs). In this article we review new insights into activity-dependent gene regulation that affects brain development and plasticity.

MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation. Single-cell RNA-sequencing (scsRNA-seq) technologies, together with computational strategies, enable exploration of miRNAs, isomiRs, and interacting RNAs at the cellular level. By integration with other miRNA-associated single-cell modalities, miRNA roles can be resolved at different stages of processing and regulation. In this review we discuss (i) single-cell experimental assays that measure miRNA and isomiR abundances, and (ii) computational methods for their analysis to investigate the mechanisms of miRNA biogenesis and post-transcriptional regulation.

Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain. The integration of single-cell technologies with genome-wide association studies (GWAS) and transcriptomic data has further advanced our understanding of cell-specific chromatin dynamics. This review discusses recent findings regarding the role played by chromatin accessibility in brain disease, highlighting the need for high-quality data and rigorous computational tools. Future directions include spatial chromatin studies and CRISPR-based functional validation to bridge genetic discovery and clinical applications, paving the way for targeted gene-regulatory therapies.

The DEAD/DEAH-box family of RNA helicases (RHs) is among the most abundant and conserved in eukaryotes. These proteins catalyze the remodeling of RNAs to regulate their splicing, stability, localization, and translation. Rare genetic variants in DEAD/DEAH-box proteins have recently emerged as being associated with neurodevelopmental disorders (NDDs). Analyses in cellular and animal models have uncovered fundamental roles for these proteins during brain development. We discuss the genetic and functional evidence that implicates DEAD/DEAH-box proteins in brain development and NDDs, with a focus on how structural insights from paralogous genes can be leveraged to advance our understanding of the pathogenic mechanisms at play.

Despite the ecological importance of the feather cover during early avian life, the events controlling the transition from natal down to juvenile feathers are poorly understood. Chen et al. demonstrate that this transition is characterized by a series of morphological and molecular changes strikingly conserved between precocial and altricial species.