Biology subjects

Persaud, M.

Publications and source records attributed to Persaud, M..

6 recordsLinked to original sources

bioRxiv2026

An interaction between HP1 and the Chromosomal Passenger Complex Initiates Acentrosomal Spindle Assembly in Drosophila oocytes

Chromosome segregation fidelity during meiosis is critical for genome integrity, with aneuploidy causing infertility, miscarriages, and congenital anomalies. In the oocytes of many species, spindle assembly occurs in the absence of centrosomes that normally function as microtubule-organizing centers at the poles. Such acentrosomal spindles are believed to pose significant challenges for accurate chromosome segregation compared to centrosomal organized spindles. Previous work in Drosophila has shown that the chromosomal passenger complex (CPC) is required for acentrosomal spindle assembly. We found that heterochromatin protein-1 (HP1) plays a critical role in regulating CPC localization and spindle assembly. Furthermore, HP1 moves to the microtubules, where it has roles in building a functional spindle and interacts with the CPC to regulate chromosome biorientation. These results indicate that spindle assembly is mediated by multiple interactions between the CPC, HP1, and the chromosomes, and provide insights into the mechanisms that restricts spindle assembly to the chromosomes in Drosophila oocytes.

cell biology↗

bioRxiv2025

Single cell mapping of the human endometrium and first trimester decidua identifies distinct epithelial and stromal cell contributions to fertility

The human endometrium undergoes dynamic changes across the menstrual cycle to establish a receptive state for embryo implantation. Using bulk and single-cell RNA sequencing, we characterized gene expression dynamics in the cycling endometrium and the decidua from early pregnancy. We are the first to demonstrate that during the mid-secretory phase--the period encompassing the window of implantation--secretory glandular epithelial cells undergo notable transcriptional changes in cell-cell communication. Through comprehensive analyses, we identified the Glandular Epithelium Receptivity Module (GERM) signature, comprising 556 genes associated with endometrial receptivity. This GERM signature was consistently perturbed across multiple datasets of endometrial samples from women with impaired fertility, validating its relevance as a marker of receptivity. In addition to epithelial changes, we observed shifts in stromal cell populations, notably involving decidual and senescent subsets, which also play key roles in modulating implantation. Together, these findings provide a high-resolution transcriptomic atlas of the receptive and early pregnant endometrium and shed light on key molecular pathways underlying successful implantation.

molecular biology↗

bioRxiv2023

A Dynamic population of prophase CENP-C is required for meiotic chromosome segregation

The centromere is an epigenetic mark that is a loading site for the kinetochore during meiosis and mitosis. This mark is characterized by the H3 variant CENP-A, known as CID in Drosophila. In Drosophila, CENP-C is critical for maintaining CID at the centromeres and directly recruits outer kinetochore proteins after nuclear envelope break down. It is not known, however, if these two functions require the same CENP-C molecules. Furthermore, in Drosophila and many other metazoan oocytes, centromere maintenance and kinetochore assembly are separated by an extended prophase. Consistent with studies in mammals, CID is relatively stable and does not need to be expressed during prophase to remain at high levels in metaphase I of meiosis. Expression of CID during prophase can even be deleterious, causing ectopic localization to non-centromeric chromatin, abnormal meiosis and sterility. In contrast to CID, maintaining high levels of CENP-C requires expression during prophase. Confirming the importance of this loading, we found CENP-C prophase loading is required for multiple meiotic functions. In early meiotic prophase, CENP-C loading is required for sister centromere cohesion and centromere clustering. In late meiotic prophase, CENP-C loading is required to recruit kinetochore proteins. CENP-C is one of the few proteins identified in which expression during prophase is required for meiotic chromosome segregation. An implication of these results is that the failure to maintain recruitment of CENP-C during the extended prophase in oocytes would result in chromosome segregation errors in oocytes. Author SummaryMeiosis in oocytes of diverse organisms, including humans and Drosophila, is characterized by a long prophase pause and a cell cycle arrest in meiosis I or meiosis II. These pauses could be a challenge for centromeres, whose components are replenished during G1, and then must remain with the chromosomes until the meiotic divisions. We have investigated the stability, prophase dynamics and function of centromere protein CENP-C. We show that CENP-C expression and loading onto centromeres during prophase is required for multiple meiotic functions. In contrast, the expression of other centromere partners CID/CENP-A and CAL1 is not required during meiotic prophase. Furthermore, expression of CID during prophase can be deleterious and result in ectopic kinetochore formation. CENP-C loading in prophase is required for sister centromere cohesion and kinetochore assembly. Our results provide the first description of CENP-C dynamics during meiosis and show that prophase expression is required for oocyte spindle assembly and function. CENP-C is among a small number of proteins that are required for the meiotic divisions but are loaded prior to prometaphase. Failure to maintain these proteins during the long prophase of oocyte meiosis may contribute to the increased aneuploidy associated with advanced maternal age.

genetics↗

bioRxiv2020

SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells

SAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function. These observations clearly establish that the absence of T592 phosphorylation cannot fully account for the restriction activity of SAMHD1. We find that concomitant SUMOylation of K595 is required to stimulate a dNTPase-independent antiviral activity.

microbiology↗

bioRxiv2020

Nuclear Import of the HIV-1 Core Precedes Reverse Transcription and Uncoating

HIV-1 particles contain a core formed by ~1500 capsid protein monomers housing viral RNA. HIV-1 core uncoating---disassembly---is required for infection. HIV-1 reverse transcription (RT) occurs before or during uncoating, but the cellular compartment where RT and uncoating occurs is unknown. Using imaging and biochemical assays to track HIV-1 capsids in nuclei during infection, we demonstrated that higher-order capsid complexes or complete cores containing viral genome are imported into nuclear compartments. Additionally, inhibition of RT that stabilizes the core during infection does not prevent capsid nuclear import; thus, RT may occur in nuclear compartments. We separated infected cells into cytosolic and nuclear fractions to measure RT during infection. Most observable RT intermediates were enriched in nuclear fractions, suggesting that most HIV-1 RT occurs in the nuclear compartment alongside uncoating. Thus, nuclear import precedes RT and uncoating, fundamentally changing our understanding of HIV-1 infection.

microbiology↗

bioRxiv2019

Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5α Binding to the viral Core

Disruption of cyclophilin A (CypA)-capsid interactions affects HIV-1 replication in human lymphocytes. To understand the mechanism, we used Jurkat cells, human PBMCs, and human CD4+ T cells. Our results showed that the inhibition of HIV-1 infection caused by disrupting CypA-capsid interactions is dependent on human TRIM5 (TRIM5hu), suggesting that TRIM5hu restricts HIV-1. Accordingly, we found that TRIM5hu binds to the HIV-1 core. Disruption of CypA-capsid interactions failed to affect HIV-1-A92E infection, correlating with the loss of TRIM5hu binding to HIV-1-A92E cores. Disruption of CypA-capsid interactions in PBMCs and CD4+ T cells had a greater inhibitory effect on HIV-1 when compared to Jurkat cells. HIV-1-A92E infection of PBMCs and CD4+ T cells was unaffected by disruption of CypA-capsid interactions. Consistent with TRIM5 restriction, disruption of CypA-capsid interactions in CD4+ T cells inhibited reverse transcription. Overall, our results showed that CypA binding to the core protects HIV-1 from TRIM5hu restriction.

microbiology↗