pals-22, A Member Of An Expanded C. elegans Gene Family, Controls Silencing Of Repetitive DNA

Abstract

Repetitive DNA sequences are subject to gene silencing in various animal species. Under specific circumstances repetitive DNA sequences can escape such silencing. For example, when exogenously added, extrachromosomal DNA sequences that are stably inherited in multicopy repetitive arrays in the nematode C. elegans are frequently silenced in the germline, whereas such silencing often does not occur in the soma. This indicates that somatic cells might utilize factors that prevent repetitive DNA silencing. Indeed, such \"anti-silencing\" factors have been revealed through genetic screens that identified mutant loci in which repetitive transgenic arrays are aberrantly silenced in the soma. We describe here a novel locus, pals-22 (for protein containing ALS2CR12 domain), required to prevent silencing of repetitive transgenes in neurons and other somatic tissue types. pals-22 deficiency also severely impacts animal vigor and confers phenotypes reminiscent of accelerated aging. We find that pals-22 is a member of a large family of divergent genes (39 members), defined by the presence of an ALS2CR12 domain. While gene family members are highly divergent, they show striking patterns of genomic clustering. The family expansion appears C. elegans-specific and has not occurred to the same extent in other nematode species. Previous transcriptome analysis has revealed that most of the pals genes are induced under stress conditions or upon infection by intracellular parasites. The transgene silencing phenotype observed upon loss of cytoplasmically localized PALS-22 protein depends on the biogenesis of small RNAs, since silencing is abolished in the RNAi defective mutant rde-4, suggesting that pals-22 might regulate RNAi dependent silencing in the cytoplasm of neurons and other tissues. We speculate that the pals gene family may be part of a species-specific cellular defense mechanism.