Morales-Oliva, Enrique et al. (2021) International Worm Meeting "GLA-3/TTP plays an important role in the germline stress response of Caenorhabditis elegans"

Navarro, Rosa E, Lascarez-Lagunas, Laura I, Salinas, Laura S, Morales-Oliva, Enrique, Damazo-Hernandez, Angel

[International Worm Meeting, 2021]

GLA-3 is the C. elegans homolog of the mammalian tristetraprolin (TTP) which encodes a protein that contains two CCCH-like zinc-finger domains that function either as transcription factors or RNA-binding proteins. This gene which encodes two splice variants GLA-3A and GLA3B and the protein is expressed in both germline and soma. Loss of gla-3 function present different alterations: protein degradation in muscle leading to a progressive loss of motility, increased germ cell death by apoptosis, severe defects in meiosis progression, reduced brood size and a low frequency of embryonic lethality. Stress granules (SG) are dynamic cytoplasmic membrane-less organelles that are formed under harsh conditions. SG are composed of mRNAs that are stalled in translation pre-initiation complexes and different types of mRNA binding proteins like TIA-1 and TTP. It has been probed by immunoprecipitation that GLA-3A-B associates with the MAP kinase protein MPK-1/ERK, which is required for pachytene progression during oogenesis, but this association is poorly understood. Additionally, in mammals was observed that TTP is phosphorilated by ERK and this modification affects SG formation, however this interaction has not been studied in C. elegans. Since TTP has been shown to be associated with SG, the aim of this work is to study the function of GLA-3 and to identify whether this protein forms SG under different adverse conditions and the role of MPK-1 / ERK in SG formation. We tested different stress conditions: heat shock (31oC for 3 hours), starvation (6 hours without bacteria) and oxidative stress (1 hour in Paraquat 0.2 mM) and evaluated SG formation using the strain tn1734 which had the protein GFP fused whit GLA-3A ([gfp::3xflag::gla-3a]). It was proved that GLA-3 express in germ line from larval stage L2 to adulthood, and in adult gonads, GFP::GLA-3A form SG under heat shock, starvation and oxidative stress. We also observed that iRNA knock-down by feeding animals with dsRNA for mpk-1 prevent the formation of GLA-3 SG. We conclude that GLA-3 is a SG component and MPK-1 participate in SG assembly.

Gramstrup Petersen, Jakob et al. (2011) International Worm Meeting "EGL-13, a SOX transcription factor, regulates neuronal cell fate determination of the BAG neurons."

Pocock, Roger, Gramstrup Petersen, Jakob

[International Worm Meeting, 2011]

Responses to changes in the oxygen environment are crucial for maintaining homeostasis and survival. In C. elegans these responses are orchestrated by soluble guanylate cyclases acting primarily in the two sets of sensory neurons - BAG and URX. The molecular factors that determine BAG cell fate are unknown. Therefore, we have conducted an EMS mutagenesis screen to isolate mutants that have lost BAG cell fate. From the screen we isolated three mutants, rp13, rp14 and rp15. rp14 has a strong Egl phenotype due to defective connection of the gonad (Cog phenotype). Due to the phenotype we hypothesized that rp14 may be an allele of egl-13. We find that egl-13::GFP is expressed in the BAG neurons and that the egl-13(ku194) allele causes 100% loss of BAG expression using the pflp-19::GFP reporter strain. egl-13 is a member of the SOX transcription factor family and has previously been described to play an essential role for the proper development of the utse1. Vertebrate homologs of EGL-13 are SOX5 and SOX6 which have been shown to be involved in chondrogenesis and cell cycle progression of neural progenitors in the chick spinal cord2,3. The discovery that egl-13 plays a role in neuronal cell fate specification in the worm might reveal that SOX5 and SOX6 also plays specific roles in the development of the human nervous system. 1Cinar, H. N., Richards, K. L., Oommen, K. S. & Newman, A. P. The EGL-13 SOX domain transcription factor affects the uterine pi cell lineages in Caenorhabditis elegans. Genetics 165, 1623-1628 (2003). 2Smits, P. et al. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell 1, 277-290, doi:S1534-5807(01)00003-X [pii] (2001). 3Martinez-Morales, P. L., Quiroga, A. C., Barbas, J. A. & Morales, A. V. SOX5 controls cell cycle progression in neural progenitors by interfering with the WNT-beta-catenin pathway. EMBO Rep 11, 466-472, doi:embor201061 [pii] 10.1038/embor.2010.61 (2010).