Publications by authors named "Maartje J Luteijn"

The Piwi-piRNA pathway represents a small RNA-based mechanism responsible for the recognition and silencing of invading DNA. Biogenesis of piRNAs (21U-RNAs) is poorly understood. In Caenorhabditis elegans, the piRNA-binding Argonaute protein PRG-1 is the only known player acting downstream from precursor transcription.

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Small-RNA-guided gene regulation is a recurring theme in biology. Animal germ cells are characterized by an intriguing small-RNA-mediated gene-silencing mechanism known as the PIWI pathway. For a long time, both the biogenesis of PIWI-interacting RNAs (piRNAs) as well as their mode of gene silencing has remained elusive.

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In recent years, the Piwi pathway has been shown to regulate the silencing of mobile genetic elements. However, we know little about how Piwi pathways impose silencing and even less about trans-generational stability of Piwi-induced silencing. We demonstrate that the Caenorhabditis elegans Piwi protein PRG-1 can initiate an extremely stable form of gene silencing on a transgenic, single-copy target.

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RNA interference (RNAi)-related pathways affect gene activity by sequence-specific recruitment of Ago proteins to mRNA target molecules. The sequence specificity of this process stems from small RNA (sRNA) co-factors bound by the Ago protein. Stability of sRNA molecules in some pathways is in part regulated by Hen1-mediated methylation of their 3' ends.

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Article Synopsis
  • Piwi-interacting RNAs (piRNAs) are small RNA molecules specific to germ cells, crucial for genome defense and germ cell development, and work through a mechanism similar to RNA interference.
  • The enzyme Hen1 adds a 2'-O-methyl modification to piRNAs, is essential for female germ line maintenance in zebrafish, and localizes to a structure called nuage, though it’s not needed for its formation.
  • In hen1 mutant testes, piRNAs undergo unwanted modifications (uridylation and adenylation), leading to reduced piRNA levels and increased expression of transposon transcripts, suggesting a mechanism for regulating piRNA stability and transposon silencing in zebrafish germ cells.
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Background Information: During development, growth cones of outgrowing neurons express proteins involved in vesicular secretion, such as SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins, Munc13 and Munc18. Vesicles are known to fuse in growth cones prior to synapse formation, which may contribute to outgrowth.

Results: We tested this possibility in dissociated cell cultures and organotypic slice cultures of two release-deficient mice (Munc18-1 null and Munc13-1/2 double null).

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