TSC22D, WNK and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation
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PROVIDER: PRJNA1122194 | ENA |
REPOSITORIES: ENA
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Project description:The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1 and NRBP1 in regulating cell volume homeostasis. Each of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK family kinases. Our study reveals that TSC22D, WNK and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.
2024-11-15 | GSE269526 | GEO
Project description:marine Metazoa environmental sample overview
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Project description:corpse decomposition and water volume
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Project description:Aneuploidy, i.e., variation in the number of individual chromosomes (chromosomal aneuploidy) or chromosome segment (segmental aneuploidy) is associated with developmental abnormalities and reduced fitness in all species examined, is the leading cause of miscarriages and mental retardations and a hallmark of cancer. Despite their documented importance in disease the effects of aneuploidies on the transcriptome remains largely unknown. Here we have examined the expression output in seven deficiency heterozygotes as single deficiencies and in all pairwise combinations. The results show that genes in one copy are buffered, i.e., are expressed above the expected 50% expression level compared to wild type and the buffering is general and not influenced by additional haploid regions. Long genes are significantly better buffered than short genes and our analysis suggests that gene length is the primary determinant for the degree of buffering. For short genes the degree of buffering depends on expression level and expression pattern. Furthermore, the results show that in deficiency heterozygotes the expression of genes involved in proteolysis is enhanced and negatively correlates with the degree of buffering. Our results suggest that proteolysis is a general response induced by aneuploidy.
2012-04-05 | GSE34400 | GEO
Project description:Aneuploidy, i.e., variation in the number of individual chromosomes (chromosomal aneuploidy) or chromosome segment (segmental aneuploidy) is associated with developmental abnormalities and reduced fitness in all species examined, is the leading cause of miscarriages and mental retardations and a hallmark of cancer. Despite their documented importance in disease the effects of aneuploidies on the transcriptome remains largely unknown. Here we have examined the expression output in seven deficiency heterozygotes as single deficiencies and in all pairwise combinations. The results show that genes in one copy are buffered, i.e., are expressed above the expected 50% expression level compared to wild type and the buffering is general and not influenced by additional haploid regions. Long genes are significantly better buffered than short genes and our analysis suggests that gene length is the primary determinant for the degree of buffering. For short genes the degree of buffering depends on expression level and expression pattern. Furthermore, the results show that in deficiency heterozygotes the expression of genes involved in proteolysis is enhanced and negatively correlates with the degree of buffering. Our results suggest that proteolysis is a general response induced by aneuploidy. We prepared total RNA from flies heterozygous for seven different deletions, Df(3R)ED10953, Df(2L)ED4559, Df(2R)ED1770, Df(2R)ED1612, Df(2L)ED3, Df(3R)ED5071 or Df(3R)ED7665 in two or three single biological replicates or in pairwise combinations, as well as from six biological replicates of wild type control flies.
2012-04-04 | E-GEOD-34400 | biostudies-arrayexpress
Project description:In this study, hepatopancreas tissues of cold-tolerant and common families of Litopenaeus vannamei were selected by the Guangxi Academy of Fishery Sciences for proteomic study. Hepatopancreas were treated at 28℃, 18℃ and 10℃ respectively based on DIA technology. There were three replicates of cold-tolerant families and common families at 28℃, 18℃ and 10℃ respectively, and each replicate contained hepatopancreas mixed samples of 6 shrimp at random. A total of 18 samples were analyzed. The original data of common families at 28℃, 18℃ and 10℃ were named Lv-C-28、Lv-C-18 and Lv-C-10 respectively, while the original data of cold-tolerant families at 28℃, 18℃ and 10℃ were named Lv-T-28、Lv-T-18 and Lv-T-10 respectively.
2023-06-09 | PXD041965 |
Project description:To become fully functional effector T cells, naïve T cells undergo a drastic metabolic status shift from quiescence to substantial biosynthesis. The synthesis of biomass initiated by T cell receptor (TCR) signals drives the cell volume increase during T cell activation (T lymphoblast), which resembles the slowest extreme of hypotonic cell swelling. However, the fundamental role of cell volume regulation in TCR signaling during T lymphoblast and its underlying mechanisms remain a long-standing enigma. Here we show that optimal T cell activation and function require appropriate cell volume regulation by regulated volume decrease (RVD) mediated via volume-regulated anion channels (VRACs) during T cell blast. Pharmacological blockade of VRACs and genetic deletion of LRRC8A in T cells, the essential component of VRACs, impair T cell activation and function, particularly under weak TCR stimulation, such as low-affinity TCR-pMHC engagement and unsaturated anti-CD3e crosslinking. Additionally, LRRC8A has distinct influences on mRNA transcriptional profiles driven by various TCR signal strengths, revealing the prominent effects of cell volume regulation for T cell functions. More importantly, LRRC8A-deficient mice have defective antiviral immunity and obstacles in effector-memory transition of CD8+ T cells. Furthermore, LRRC8A escorts the thymic selection of T cells and shapes the T cell repertoire in the thymus. Mechanistically, LRRC8A governs stringent cell volume increase via RVD during T cell blast induced by activation-driven intracellular osmolytes accumulation to keep the proximal TCR signaling molecules at adequate density. T cell blast driven by TCR signal feedbacks to control T cell activation. Together, our results reveal a previously unappreciated layer of T cell activation regulation that LRRC8A acts as a cell volume controlling "valve" to facilitate T cell activation and function
2023-09-23 | GSE243574 | GEO
Project description:Microarrays were used to examine gene expression changes in the surgical resections of high-grade serous ovarian cancer patients exhibiting clinically distinct levels of ascites volume. The present studies primary aim was to determine if there is a molecular gene expression difference between the patients presenting at time of surgery when high volumes ascites cases were compared to those with low volume ascites. The secondary aim was to determine what relevance this difference, if found, has to previously discovered molecular sub-types of high grade serous ovarian cancer. Total RNA obtained from snap-frozen stage III-IV high-grade serous ovarian cancer patients presenting with low volume (<=200 cc) or high volume (>=1000 cc) ascites volume.
2014-10-01 | E-GEOD-51831 | biostudies-arrayexpress
Project description:Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human. While gene regulation is a multi-step process, the majority of research concerning divergence in gene regulation among primates has focused on transcription. To gain a comprehensive view of gene regulation, we surveyed genome-wide ribosome occupancy, which reflects levels of protein translation, in lymphoblastoid cell lines derived from human, chimpanzee and rhesus macaque. We further integrated mRNA and protein level measurements collected from matching cell lines. We find that, in addition to transcriptional regulation, the major factor determining protein level divergence between human and closely related species is post-translational buffering. Inter-species divergence in transcription is generally propagated to the level of protein translation. In contrast, gene expression divergence is often attenuated post-translationally, potentially mediated through post-translational modifications. Results from our analysis indicate that post-translational buffering is a conserved mechanism that led to relaxation of selective constraint on transcript levels in humans.
2018-05-10 | GSE71808 | GEO