Biology subjects

T, A.

Publications and source records attributed to T, A..

2 recordsLinked to original sources

bioRxiv2025

Mon1-Rab7 axis is essential for transport, localization and anchoring of oskar mRNA

Asymmetric localization of oskar mRNA to the posterior of the oocyte is a complex process driven by autonomous and non-cell autonomous mechanisms. The former includes Oskar protein that reinforces localization and anchoring of its mRNA through activation of endocytosis and regulation of actin cytoskeleton; the latter includes signals from the posterior follicle cells (PFCs) that regulates microtubule orientation for polarized transport. Here we identify Monensin Sensitivity 1 (Mon1), as a novel factor regulating anterior-posterior (A-P) patterning. Mon1 is an evolutionarily conserved activator of Rab7-a key regulator of the endo-lysosomal pathway. Embryos lacking maternal mon1 (mon1m) show mislocalized oskar and bicoid mRNAs leading to loss of patterning and lethality. In the mutant oocyte Staufen appears clumpy and the levels of Oskar protein and Par-1 is significantly reduced. Abnormal actin rings are seen in the ooplasm. Driving expression of mon1 in the germline rescues these phenotypes and restores viability. In contrast, expression in the PFC predominantly rescues the Par-1 phenotype with a modest effect on viability. We demonstrate that oskar mRNA interacts with Rab7 suggesting possible role for the Mon1-Rab7 axis in the transport of oskar. We show that Mon1 in the PFCs, regulates PIP2 levels to influence accumulation of Par-1 in the oocyte. We propose that Mon1 regulates oskar localization in two distinct ways: cell autonomously in the germline by regulating Rab7, and non-cell autonomously through the PFCs by regulating accumulation of Par-1. Summary statementMon1, an established Rab converter, has roles in embryonic axial patterning, modulating transport, localisation and anchoring of posteriorly localised mRNA during oocyte maturation. Mon1 influence is both cell autonomous, from within the oocyte and non-cell autonomous, through posterior follicle cells.

developmental biology↗

bioRxiv2024

Theileria annulata Infection Promotes p53 suppression, Genomic Instability and DNA deaminase APOBEC3H upregulation leading to cancer-like phenotype in host cells

Theileria annulata-infected host leukocytes display cancer-like phenotypes, though the precise mechanism is yet to be fully understood. The occurrence of cancer-like phenotypes in Theileria-infected leukocytes may be attributed to various factors, including genomic instability and acquired mutations, a crucial trait that underpins the genetic foundation of cancer. This paper presents WGS data and bioinformatic analyses to reveal point mutations and large-scale alterations in six clinically relevant T. annulata-infected cell lines. We identified 7867 exon-linked somatic mutations common to all cell lines, and cancer association analysis showed significant accumulation in oncogenes (FLT4, NOTCH2, MAP3K1, DAXX, FCGR2B, ROS1) and tumor suppressor genes (BARD1, KMT2C, GRIN2A, BAP1) implicated in established critical cancer processes. We demonstrated that a crizotinib-induced blockade of the ROS1 oncogenic protein, which harbored the most mutations, led to the death of infected leukocytes. This is consistent with the significant role of ROS1 in parasite-induced leukocyte transformation. In addition, we found somatic mutations in genes involved in genome instability and the DDR pathway. Our findings support the notion that ROS1 and Nutulin 3a are valid targets for intervention, and the suppression of TP53, a crucial tumor suppressor gene, may play a significant role in cell immortalization. We also show that upon infection with the parasite, bovine cells upregulate the expression of APOBEC3H, a DNA mutator likely responsible for the detected mutations. Our study highlights how T. annulata transforms leukocytes to gain selective advantage via mutation, and our observations could steer future research towards a mechanistic understanding of disease pathogenesis.

cell biology↗