Germline immortality relies on TRIM32-mediated turnover of a maternal mRNA activator in .

Sci Adv

Developmental Genetics, Institute of Biology, Martin Luther University Halle-Wittenberg (MLU), Weinbergweg 10, Halle (Saale) 06120, Germany.

Published: October 2022

How the germ line achieves a clean transition from maternal to zygotic gene expression control is a fundamental problem in sexually reproducing organisms. Whereas several mechanisms terminate the maternal program in the soma, this combined molecular reset and handover are poorly understood for primordial germ cells (PGCs). Here, we show that GRIF-1, a TRIM32-related and presumed E3 ubiquitin ligase in , eliminates the maternal cytoplasmic poly(A) polymerase (cytoPAP) complex by targeting the germline-specific intrinsically disordered region of its enzymatic subunit, GLD-2, for proteasome-mediated degradation. Interference with cytoPAP turnover in PGCs causes frequent transgenerational sterility and, eventually, germline mortality. Hence, positively acting maternal RNA regulators are cleared via the proteasome system to avoid likely interference between maternal and zygotic gene expression programs to maintain transgenerational fertility and acquire germline immortality. This strategy is likely used in all animals that preform their immortal germ line via maternally inherited germplasm determinants.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565796PMC
http://dx.doi.org/10.1126/sciadv.abn0897DOI Listing

Publication Analysis

Top Keywords

germline immortality
8
maternal zygotic
8
zygotic gene
8
gene expression
8
maternal
6
immortality relies
4
relies trim32-mediated
4
trim32-mediated turnover
4
turnover maternal
4
maternal mrna
4

Similar Publications

Proper formation and specification of Primordial Germ Cells (PGCs) is of special significance as they gradually transform into Germline Stem Cells (GSCs) that are ultimately responsible for generating the gametes. Intriguingly, not only the PGCs constitute the only immortal cell type but several specific determinants also underlying PGC specification such as Vasa, Nanos and Germ-cell-less are conserved through evolution. In , PGC formation and specification depends on two independent factors, the maternally deposited specialized cytoplasm (or germ plasm) enriched in germline determinants, and the mechanisms that execute the even partitioning of these determinants between the daughter cells.

View Article and Find Full Text PDF

Nuclear RNAi in C. elegans induces a set of transgenerationally heritable marks of H3K9me3, H3K23me3, and H3K27me3 at the target genes. The function of H3K23me3 in the nuclear RNAi pathway is largely unknown due to the limited knowledge of H3K23 histone methyltransferase (HMT).

View Article and Find Full Text PDF

Survey for Activating Oncogenic Mutation Variants in Metazoan Germline Genes.

J Mol Evol

December 2024

National Cancer Institute, 9609 Medical Center Drive, 5E-132, Rockville, MD, 20850, USA.

Most cancers present with mutations or amplifications in distinctive tumor promoter genes that activate principal cell-signaling cascades promoting cell proliferation, dedifferentiation, cell survival, and replicative immortality. Somatic mutations found in this these driver proto-oncogenes invariably result in constitutive activation of the encoded protein. A salient feature of the activating mutations observed throughout many thousands of clinical tumor specimens reveals these driver missense mutations are recurrent and restricted to just one or very few codons of the entire gene, suggesting they have been positively selected during the course of tumor development.

View Article and Find Full Text PDF
Article Synopsis
  • This study explores the role of a newly identified histone methyltransferase, SET-21, in the nuclear RNA interference (RNAi) pathway, which marks genes with H3K9me3, H3K23me3, and H3K27me3 for gene silencing.
  • The researchers found that SET-21 cooperatively works with another methyltransferase, SET-32, to deposit H3K23me3 at targeted genes, enhancing germline stability and transgenerational gene silencing, especially under stress conditions.
  • The double mutant strain, lacking both SET-21 and SET-32, shows greater germline mortality at high temperatures compared to single mutants, suggesting a significant role for these proteins
View Article and Find Full Text PDF

Integrating Microarray Data and Single-Cell RNA-Seq Reveals Key Gene Involved in Spermatogonia Stem Cell Aging.

Int J Mol Sci

October 2024

Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.

The in vitro generation of spermatogonial stem cells (SSCs) from embryonic stem cells (ESCs) offers a viable approach for addressing male infertility. A multitude of molecules participate in this intricate process, which requires additional elucidation. Despite the decline in SSCs in aged testes, SSCs are deemed immortal since they can multiply for three years with repeated transplantation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!