Trends in Genetics最新文献

Investigating RNA dynamics is crucial for uncovering fundamental mechanisms, such as alternative splicing, RNA stability, and post-transcriptional modifications, all processes with implications for identifying therapeutic targets and advancing knowledge of cellular function and regulation. Advances in long-read sequencing technologies, particularly from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), offer unprecedented insights into RNA dynamics at single molecule and single nucleotide resolutions. In this review, we examine protocols and methods for analyzing RNA dynamics, focusing on isoform detection, poly(A) tail length quantification, and mapping of RNA modifications. We envision that these high-throughput, transcriptome-wide data sets, combined with integrated software systems, will transform workflows for studying single molecule RNA dynamics. Such advances will help unravel the complexities of gene regulation and deepen our understanding of cellular processes.

Cis-regulatory elements (CREs) are critical sequence determinants for spatiotemporal control of gene expression. Genetic variants within CREs have driven phenotypic transitions from wild to cultivated plants during domestication. This review summarizes our current understanding of genetic variants within CREs involved in plant domestication. We also propose avenues for studies to expand our understanding of both CRE biology and domestication processes, such as examining primary mechanisms that generate CRE genetic variants during plant domestication and investigating the roles of CREs in domestication syndrome. Additionally, we discuss existing challenges and highlight future opportunities for exploring CREs in plant domestication, emphasizing the potential of modifying CREs to contribute to crop improvement.

Epigenetic regulation plays a pivotal role in orchestrating early embryo development, guiding the transition from a totipotent zygote to a complex multicellular organism. This review summarizes the dynamic landscape of epigenetic reprogramming during preimplantation embryo development, emphasizing the interplay between DNA methylation, histone modifications, higher-order chromatin, transposable elements (TEs), and RNA modifications in resetting the parental epigenome. We also summarize the abnormal epigenetic reprogramming observed in somatic cell nuclear transfer (SCNT) and assisted reproductive technologies (ART), as well as clinical disorders resulting from these epigenetic defects, and discuss potential therapeutic strategies and future research directions. We seek to elucidate the role of epigenetic modifications in developmental defects, offering perspectives to enhance both developmental biology studies and clinical applications of assisted reproduction.

The translation of genome sequence variation into proteoform diversity lies at the heart of the central dogma. In a recent study, Zhu et al. developed a graph-based algorithm that models gene expression complexity, providing an exhaustive answer to the question: 'Given a set of genomic variants, which proteins might one see?'

Among the pervasive transcripts from eukaryotic genomes, a novel subset, referred to as architectural RNAs (arcRNAs), has an essential role in assembling membraneless organelles (MLOs). These arcRNAs sequester specific RNA-binding proteins (RBPs) and promote phase separation through multivalent interactions. NEAT1_2, an archetypal arcRNA, serves as a blueprint for paraspeckle architecture, characterized by a shell-and-core micelle-like configuration and immiscibility with other MLOs, relying on the cooperative contributions of distinct modular RNA domains. arcRNAs regulate gene expression through three of MLO action modes (crucible, sponge, and hub), guided by the functional blueprints embedded in arcRNA sequences. Advanced high-throughput analyses have identified thousands of arcRNA candidates, underscoring their potential in organizing transient intracellular compartments and driving dynamic cellular processes.

Clustered regularly interspaced short palindromic repeats (CRISPR) technologies have rapidly evolved beyond genome editing, transforming fields such as molecular diagnostics, biosensing, transcriptional regulation, molecular imaging, protein interaction mapping, and single-cell analysis. Emerging CRISPR-based diagnostics harness the collateral cleavage activity of CRISPR-associated (Cas) enzymes for rapid nucleic acid detection. Advanced biosensors extend CRISPR's capabilities to detect ions, metabolites, and proteins by integrating synthetic biology components. Catalytically inactive Cas proteins enable precise gene regulation and live-cell imaging of nucleic acids, whereas CRISPR-guided proximity labeling has revolutionized the mapping of biomolecular interactions. Recent single-cell CRISPR screens provide unprecedented resolution of cellular heterogeneity. Future research will focus on overcoming current limitations. The integration of CRISPR technologies with artificial intelligence (AI), spatial omics, and microfluidics is expected to further amplify their impact.

Male infertility is a global health problem, affecting up to 6% of reproductive age men worldwide. It has an enormous personal and societal burden, along with public health implications beyond the inability to reproduce, including reduced future health and longevity. While the impact of infertility has long been appreciated, the molecular architecture of the disease is largely unknown. Nevertheless, the past decade has witnessed significant advances in our understanding of the molecular basis of male infertility. Here, we describe the contributions of genetic and epigenetic mechanisms to infertility-associated phenotypes and their impact beyond reproduction. This review focuses on progress in understanding defects in sperm production and function, and the potential impact of these advances on diagnosis, treatments, and improved health.

How did the chromatin folding mechanisms controlling gene regulation emerge during animal evolution? Kim et al. surveyed chromatin folding at high-resolution in unicellular relatives of animals as well as non-bilaterian animal lineages. They found that chromatin loops appeared concomitantly with complex gene regulation and uncovered an unexpected diversity of chromatin looping mechanisms.

Synthetic DNA technologies may eventually enable the creation of synthetic gametes, which would offer precise control over genetic inheritance. This possibility raises profound ethical questions about human identity, genetic selection, and evolutionary boundaries. While synthetic gametes sidestep person-affecting ethical concerns, they present challenges for balancing reproductive autonomy and minimizing heritable disease, prompting interdisciplinary reflection.