Migration of Influenza Virus Nucleoprotein into the Nucleolus Is Essential for Ribonucleoprotein Complex Formation

Influenza A virus ribonucleoprotein complex (RNP) is responsible for viral genome replication, thus playing essential roles in the virus life cycle. RNP formation occurs in the nuclei of infected cells; however, little is known about the nuclear domains involved in this process.

Annual Long-Distance Migration Strategies and Home Range of Chinese Sparrowhawk (Accipiter soloensis) from South China

From 2018 to 2019, two Chinese Sparrowhawks (Bird 01, male; Bird 02, female), Accipiter soloensis, were captured and fitted with Global Positioning System (GPS) loggers in order to identify summering and wintering sites, migration routes, and stop-over sites. The Chinese Sparrowhawks were first fitted with backpack solar GPS satellite trackers in China in order to explore their migration routes. The two Chinese Sparrowhawks successfully completed their migration from southern China, through Nanning city of Guangxi province, China, to Vietnam, Laos, Myanmar, Thailand, Malaysia, and Singapore and finally arriving in Indonesia, where they stayed until the March of the following year. They then returned to China along the original route, arriving in Changsha city, Hunan province, China. The two individuals traveled more than 4000–5000 km. For the first time, telemetry data demonstrate, the linkages between their Indonesia wintering sites, their stop-over sites in Southeast Asia, and their breeding/summering sites near south Yangtze River in the south-central part of China. During this long-distance migration, 2653 bird satellite sites were received. The autumn migration durations for the two Chinese Sparrowhawks were 84 days and 50 days, respectively, compared to 83 days and 49 days in spring. The median stop-over duration was 12.7 and 9.3 days, respectively and the median speed of travel was 74.2 km/day during the autumn migration and 73.9 km/day during the spring migration. Furthermore, two and one stop-over sites and one and three stop-over sites were used during the autumn and spring migrations of Chinese Sparrowhawks 01 and 02, respectively. The Chinese Sparrowhawks migrated long distances and used stop-over sites during their migration. Based on the home range analysis, we can conclude that Chinese Sparrowhawks reach their maximum home range in the summer and have multiple nuclear domains.

Long Noncoding RNAs—Crucial Players Organizing the Landscape of the Neuronal Nucleus

The ability to regulate chromatin organization is particularly important in neurons, which dynamically respond to external stimuli. Accumulating evidence shows that lncRNAs play important architectural roles in organizing different nuclear domains like inactive chromosome X, splicing speckles, paraspeckles, and Gomafu nuclear bodies. LncRNAs are abundantly expressed in the nervous system where they may play important roles in compartmentalization of the cell nucleus. In this review we will describe the architectural role of lncRNAs in the nuclei of neuronal cells.

Power-law behavior of transcription factor dynamics at the single-molecule level implies a continuum affinity model

Single-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the diffusion and binding behavior of these proteins in the nuclear environment. Dwell time distributions obtained by SMT for most TFs appear to follow bi-exponential behavior. This has been ascribed to two discrete populations of TFs—one non-specifically bound to chromatin and another specifically bound to target sites, as implied by decades of biochemical studies. However, emerging studies suggest alternate models for dwell-time distributions, indicating the existence of more than two populations of TFs (multi-exponential distribution), or even the absence of discrete states altogether (power-law distribution). Here, we present an analytical pipeline to evaluate which model best explains SMT data. We find that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution of dwell-times, blurring the temporal line between non-specific and specific binding, suggesting that productive binding may involve longer binding events than previously believed. From these observations, we propose a continuum of affinities model to explain TF dynamics, that is consistent with complex interactions of TFs with multiple nuclear domains as well as binding and searching on the chromatin template.

Nuclear long non-coding RNAs as epigenetic regulators in cancer

Background: Transcriptome analyses have revealed the presence of numerous long non-coding RNAs (lncRNAs) in mammalian cells. Many lncRNAs are expressed in development-, differentiation-, and disease-specific manners, suggesting their importance as cell regulators. Some nuclear lncRNAs are bound to specific genomic loci, either near or distant from their own transcription sites, and regulate gene expression in cis or trans. These lncRNAs recruit epigenetic factors, including the DNA methyl transferase and histone modification complex, and mediate both the 3D genome structure and nuclear domains. LncRNAs are now considered as an emerging member of epigenetic regulators. LncRNAs are dysregulated in various types of cancer, and act as either oncogenic or tumor-suppressing factors. They are involved in virtually all of the cancer hallmarks, and are potential diagnostic markers and therapeutic targets. Objective: In this review, we describe several representative lncRNAs and provide a current overview of the mechanisms by which lncRNAs participate in epigenetic regulation and contribute to cancer development.

The Role of ND10 Nuclear Bodies in Herpesvirus Infection: A Frenemy for the Virus?

Nuclear domains 10 (ND10), a.k.a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses. The diversity and dynamics of ND10 residents enable them to play seemingly opposite roles under different physiological conditions. Although the molecular mechanisms are not completely clear, the pro- and anti-cancer effects of ND10 have been well established in tumorigenesis. However, in herpesvirus research, until the recently emerged evidence of pro-viral contributions, ND10 nuclear bodies have been generally recognized as part of the intrinsic antiviral defenses that converge to the incoming viral DNA to inhibit the viral gene expression. In this review, we evaluate the newly discovered pro-infection influences of ND10 in various human herpesviruses and analyze their molecular foundation along with the traditional antiviral functions of ND10. We hope to shed light on the explicit role of ND10 in both the lytic and latent cycles of herpesvirus infection, which is imperative to the delineation of herpes pathogenesis and the development of prophylactic/therapeutic treatments for herpetic diseases.

Helicase LSH/Hells regulates kinetochore function, histone H3/Thr3 phosphorylation and centromere transcription during oocyte meiosis

Centromeres are epigenetically determined nuclear domains strictly required for chromosome segregation and genome stability. However, the mechanisms regulating centromere and kinetochore chromatin modifications are not known. Here, we demonstrate that LSH is enriched at meiotic kinetochores and its targeted deletion induces centromere instability and abnormal chromosome segregation. Superresolution chromatin analysis resolves LSH at the inner centromere and kinetochores during oocyte meiosis. LSH knockout pachytene oocytes exhibit reduced HDAC2 and DNMT-1. Notably, mutant oocytes show a striking increase in histone H3 phosphorylation at threonine 3 (H3T3ph) and accumulation of major satellite transcripts in both prophase-I and metaphase-I chromosomes. Moreover, knockout oocytes exhibit centromere fusions, ectopic kinetochore formation and abnormal exchange of chromatin fibers between paired bivalents and asynapsed chromosomes. Our results indicate that loss of LSH affects the levels and chromosomal localization of H3T3ph and provide evidence that, by maintaining transcriptionally repressive heterochromatin, LSH may be essential to prevent deleterious meiotic recombination events at repetitive centromeric sequences.

A role of territory formation in disruption of heterologous pairings in Drosophila male meiosis

Pairings between heterologous chromosomes in meiosis can lead to nondisjunction and the production of aneuploid gametes. To minimize these aberrant outcomes, organisms have evolved mechanisms to disrupt such improper pairings prior to orientation and segregation. In the male fruit fly, Drosophila melanogaster, bivalents segregate to distinct nuclear domains in prophase I, and it has been proposed that the formation of these distinct territories may play a role in disrupting interactions between limited homologies on heterologous chromosomes. To test this, we used fluorescent in situ hybridization to examine pairing between the X chromosome and Dp(1;3) chromosomes in which a segment of the X had been transposed to chromosome 3. We found that 120kb of homology was sufficient to insure nearly complete pairing but was not sufficient to direct merotelic segregation of the paired elements, suggesting that such pairings were being disrupted. We compared the perdurance of X / Dp(1;3) pairings to that of X / Dp(1;Y) pairings (in which homologs are paired),and found that heterologous pairings were disrupted at a higher frequency at the S2b stage of prophase I, the stage at which territory formation is initiated. Our results support the model that movement of bivalents into distinct domains in prophase I provides a mechanism to disrupt pairings between limited regions of homology, and thus may be one means of preventing improper segregation of heterologs in this organism.

Emerging Roles of Long Non-Coding RNAs in Renal Fibrosis

Renal fibrosis is an unavoidable consequence that occurs in nearly all of the nephropathies. It is characterized by a superabundant deposition and accumulation of extracellular matrix (ECM). All compartments in the kidney can be affected, including interstitium, glomeruli, vasculature, and other connective tissue, during the pathogenesis of renal fibrosis. The development of this process eventually causes destruction of renal parenchyma and end-stage renal failure, which is a devastating disease that requires renal replacement therapies. Recently, long non-coding RNAs (lncRNAs) have been emerging as key regulators governing gene expression and affecting various biological processes. These versatile roles include transcriptional regulation, organization of nuclear domains, and the regulation of RNA molecules or proteins. Current evidence proposes the involvement of lncRNAs in the pathologic process of kidney fibrosis. In this review, the biological relevance of lncRNAs in renal fibrosis will be clarified as important novel regulators and potential therapeutic targets. The biology, and subsequently the current understanding, of lncRNAs in renal fibrosis are demonstrated—highlighting the involvement of lncRNAs in kidney cell function, phenotype transition, and vascular damage and rarefaction. Finally, we discuss challenges and future prospects of lncRNAs in diagnostic markers and potential therapeutic targets, hoping to further inspire the management of renal fibrosis.

Tidying-up the plant nuclear space: domains, functions, and dynamics

Understanding how the packaging of chromatin in the nucleus is regulated and organized to guide complex cellular and developmental programmes, as well as responses to environmental cues is a major question in biology. Technological advances have allowed remarkable progress within this field over the last years. However, we still know very little about how the 3D genome organization within the cell nucleus contributes to the regulation of gene expression. The nuclear space is compartmentalized in several domains such as the nucleolus, chromocentres, telomeres, protein bodies, and the nuclear periphery without the presence of a membrane around these domains. The role of these domains and their possible impact on nuclear activities is currently under intense investigation. In this review, we discuss new data from research in plants that clarify functional links between the organization of different nuclear domains and plant genome function with an emphasis on the potential of this organization for gene regulation.