Solid tumors as well as leukemias and lymphomas show striking changes in nuclear structure including nuclear size and shape, the number and size of nucleoli, and chromatin texture. These alterations have been used in cancer diagnosis and might be related to the altered functional properties of cancer cells. The nuclear matrix (NM) represents the structural composition of the nucleus and consists of nuclear lamins and pore complexes, an internal ribonucleic protein network, and residual nucleoli. In the nuclear microenvironment, the NM is associated with multi-protein complexes, such as basal transcription factors, signaling proteins, histone-modifying factors, and chromatin remodeling machinery directly or indirectly through scaffolding proteins. Therefore, alterations in the composition of NM could result in altered DNA topology and changes in the interaction of various genes, which could then participate in a cascade of the cancer process. Using an androgen-sensitive prostate cancer cell line, LNCaP, and its androgen-independent derivative, LN96, conventional 2D-proteomic analysis of the NM proteins revealed that purine-rich element binding protein alpha (PURα) was detected in the NM proteins and differentially expressed between the cell lines. In this article, we will review the potential role of the molecule in prostate cancer.

Matrin-3 (MATR3) was initially discovered as a component of the nuclear matrix about thirty years ago. Since then, accumulating studies have provided evidence that MATR3 not only plays a structural role in the nucleus, but that it is also an active protein involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in the nucleus and cytoplasm. Furthermore, MATR3 may play a critical role in various cellular processes, including DNA damage response, cell proliferation, differentiation, and survival. In addition to the revelation of its biological role, recent studies have reported MATR3\'s involvement in the context of various diseases, including neurodegenerative and neurodevelopmental diseases, as well as cancer. Moreover, sequencing studies of patients revealed a handful of disease-associated mutations in MATR3 linked to amyotrophic lateral sclerosis (ALS), which further elevated the gene\'s importance as a topic of study. In this review, we synthesize the current knowledge regarding the diverse functions of MATR3 in DNA- and RNA-related processes, as well as its involvement in various diseases, with a particular emphasis on ALS.

Sad1 and UNC84 (SUN) and Klarsicht, ANC-1, and Syne homology (KASH) proteins interact at the nuclear periphery to form the linker of nucleoskeleton and cytoskeleton (LINC) complex, spanning the nuclear envelope (NE) and connecting the cytoskeleton with the nuclear interior. It is now well-documented that several cellular functions depend on LINC complex formation, including cell differentiation and migration. Intriguingly, recent studies suggest that SUN proteins participate in cellular processes where their association with KASH proteins may not be required. Building on this recent research, we elaborate on the hypothesis that SUN proteins may perform LINC-independent functions and discuss the modalities that may allow SUN proteins to function at the INM when they are not forming LINC complex.

Nuclear migration through narrow constrictions is important for development, metastasis, and proinflammatory responses. Studies performed in tissue culture cells have implicated linker of nucleoskeleton and cytoskeleton (LINC) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei in vivo. In Caenorhabditis elegans larvae, six pairs of hypodermal P cells migrate from lateral to ventral positions through a constricted space between the body wall muscles and the cuticle. P-cell nuclear migration is mediated in part by LINC complexes using a microtubule-based pathway and by an independent CDC-42/actin-based pathway. However, when both LINC complex and actin-based pathways are knocked out, many nuclei still migrate, suggesting the existence of additional pathways. Here, we show that FLN-2 functions in a third pathway to mediate P-cell nuclear migration. The predicted N-terminal actin-binding domain in FLN-2 that is found in canonical filamins is dispensable for FLN-2 function; this and structural predictions suggest that FLN-2 does not function as a filamin. The immunoglobulin-like repeats 4-8 of FLN-2 were necessary for P-cell nuclear migration. Furthermore, in the absence of the LINC complex component unc-84, fln-2 mutants had an increase in P-cell nuclear rupture. We conclude that FLN-2 functions to maintain the integrity of the nuclear envelope in parallel with the LINC complex and CDC-42/actin-based pathways to move P-cell nuclei through constricted spaces.

HSV-1 major tegument protein VP22 is present in multiple subcellular locations in the late stages of productive viral infection. We initially performed a detailed time course experiment and observed that VP22 was detected in nuclear and nuclear matrix fractions as early as 4 hpi. The goal was to determine the fate of virion-derived incoming VP22, and we report the following: (i) VP22 was detected in nuclear matrix fractions 1 hpi. (ii) In the presence of cycloheximide (CHX), VP22 was present in the nuclear matrix 1-6 hpi, demonstrating the stability of the protein. (iii) The nuclear matrix targeting of VP22 occurred in infected Vero, HEp-2, and human mammary epithelial (HME) cells and following synchronized infection. Based on these results, we conclude that (iv) VP22 targets the nuclear matrix and chromatin upon entry into cells during productive HSV-1 infection.

The hierarchical structure of eukaryotic genomes has regulatory layers, one of them being epigenetic \"indexing\" of the genome that leads to cell-type-specific patterns of gene expression. By establishing loops and defining chromatin domains, cells can achieve coordinated control over multi-locus segments of the genome. This is thought to be achieved using scaffold/matrix attachment regions (S/MARs) that establish structural and functional loops and topologically associating domains (TADs) that define a self-interacting region of the genome. Large-scale genome-wide mapping of S/MARs has begun to uncover these aspects of genome organization. A recent genome-wide study showed the association of transposable elements (TEs) with a significant fraction of S/MARs, suggesting that the multitude of TE-derived repeats constitute a class of anchorage sites of chromatin loops to nuclear architecture. In this study, we provide an insight that TE-driven dispersal of S/MARs has the potential to restructure the chromosomes by creating novel loops and domains. The combination of TEs and S/MARs, as elements that can hop through the genome along with regulatory capabilities, may provide an active mechanism of genome evolution leading to the emergence of novel features in biological systems. The significance is that a genome-wide study mapping developmental S/MARs reveals an intriguing link between these elements and TEs. This article highlights the potential of the TE-S/MAR combination to drive evolution by restructuring and shaping the genome.

The nuclear matrix is a nuclear compartment that has diverse functions in chromatin regulation and transcription. However, how this structure influences epigenetic modifications and gene expression in plants is largely unknown. In this study, we show that a nuclear matrix binding protein, AHL22, together with the two transcriptional repressors FRS7 and FRS12, regulates hypocotyl elongation by suppressing the expression of a group of genes known as SMALL AUXIN UP RNAs (SAURs) in Arabidopsis thaliana. The transcriptional repression of SAURs depends on their attachment to the nuclear matrix. The AHL22 complex not only brings these SAURs, which contain matrix attachment regions (MARs), to the nuclear matrix, but it also recruits the histone deacetylase HDA15 to the SAUR loci. This leads to the removal of H3 acetylation at the SAUR loci and the suppression of hypocotyl elongation. Taken together, our results indicate that MAR-binding proteins act as a hub for chromatin and epigenetic regulators. Moreover, we present a mechanism by which nuclear matrix attachment to chromatin regulates histone modifications, transcription, and hypocotyl elongation.

There is growing evidence that X-chromosome inactivation is driven by phase-separated supramolecular assemblies. However, among the many proteins recruited to the inactive X chromosome by Xist long non-coding RNA, so far only a minority (CIZ1, CELF1, SPEN, TDP-43, MATR3, PTBP1, PCGF5) have been shown to form Xist-seeded protein assemblies, and of these most have not been analyzed in detail. With focus on CIZ1, here we describe 1) the contribution of intrinsically disordered regions in RNA-dependent protein assembly formation at the inactive X chromosome, and 2) enrichment, distribution, and function of proteins within Xist-seeded assemblies.

As an important posttranslational modification, SUMOylation plays critical roles in almost all biological processes. Although it has been well-documented that SUMOylated proteins are mainly localized in the nucleus and have roles in chromatin-related processes, we showed recently that the SUMOylation machinery is actually enriched in the nuclear matrix rather than chromatin. Here, we provide compelling biochemical, cellular imaging and proteomic evidence that SUMOylated proteins are highly enriched in the nuclear matrix. We demonstrated that inactivation of SUMOylation by inhibiting SUMO-activating E1 enzyme or KO of SUMO-conjugating E2 enzyme UBC9 have only mild effect on nuclear matrix composition, indicating that SUMOylation is neither required for nuclear matrix formation nor for targeting proteins to nuclear matrix. Further characterization of UBC9 KO cells revealed that loss of SUMOylation did not result in significant DNA damage, but led to mitotic arrest and chromosome missegregation. Altogether, our study demonstrates that SUMOylated proteins are selectively enriched in the nuclear matrix and suggests a role of nuclear matrix in mediating SUMOylation and its regulated biological processes.

The linkers of the nucleoskeleton and cytoskeleton (LINC) complex comprises Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, whose conserved interactions provide a physical coupling between the cytoskeleton and the nucleoskeleton, thereby mediating the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. Recent studies have suggested a higher-order assembly of SUN and KASH instead of a more widely accepted linear trimer model for the LINC complex. In the present study, we use molecular dynamics simulations to investigate the mechanism of force transfer across the two proposed models of LINC complex assembly, namely the 3:3 linear trimer model and the 6:6 higher-order model. Employing steered molecular dynamics simulations with various structures using forces at different rates and directions, we examine the structural stability of the two models under various biologically relevant conditions. Our results suggest that both models can withstand and transfer significant levels of force while retaining their structural integrity. However, the force response of various SUN/KASH assemblies depend on the force direction and pulling rates. Slower pulling rates result in higher mean square fluctuations of the 3:3 assembly compared to the fast pulling. Interestingly, the 6:6 assembly tends to provide an additional range of motion flexibility and might be more advantageous to the structural rigidity and pliability of the nuclear envelope. These findings offer insights into how the SUN and KASH proteins maintain the structural integrity of the nuclear membrane.