Homophthalic anhydride (HPA) dimerizes under the influence of base to provide, sequentially, the (3-4’)-C-acyl dimer, a pair of chiral diastereomeric bis(lactones), 3-(2-carboxybenzyl)isocoumarin-4-carboxylic acid, and finally, 3-(2-carboxybenzyl)isocoumarin. The structures of the bis(lactones) were misassigned in 1970 based on the (presumed) cis thermal decarboxylative elimination reaction of the lower melting one. The preferred pathway should be trans-anti, however, and crystallographic analysis of one of the bis(lactones) reverses the earlier assignment. The formal cycloaddition reaction of HPA with imines occurs in preference to HPA dimerization; the mechanistic implications of this reactivity difference are discussed.
Despite the prominent role of endo-siRNAs in transposon silencing, their expression is not limited to these “nonself” DNA elements. Transcripts of protein-coding genes (“self” DNA) in some cases also produce endo-siRNAs in yeast, plants, and animals (Piatek and Werner 2014). How cells distinguish these two populations of siRNAs to prevent unwanted silencing of active genes in animals is not well understood. To address this question, we inserted various self-gene or gfp fragments into an LTR retrotransposon that produces abundant siRNAs and examined the propensity of these gene fragments to produce ectopic siRNAs in C. elegans germline. We found that fragments of germline genes are generally protected from production of ectopic siRNAs. This phenomenon, which we termed “target-directed suppression of siRNA production” (or siRNA suppression), is dependent on the germline expression of target mRNA and requires germline P-granule components. We found that siRNA suppression can also occur to naturally produced endo-siRNAs. We suggest that siRNA suppression plays an important role in regulating siRNA expression and preventing self-genes from aberrant epigenetic silencing.
Despite their prominent role in transposon silencing, expression of endo-siRNAs is not limited to the non-self DNA elements. Transcripts of protein-coding genes (self DNA) in some cases also produce endo-siRNAs in yeast, plants, and animals. How cells distinguish these two populations of siRNAs to prevent unwanted silencing of self-genes in animals is not well understood. To address this question, we examined the expression of ectopic siRNAs from an LTR retrotransposon in C. elegans germline. We found that the abundance of ectopic siRNAs was dependent on their homologous target genes: ectopic siRNAs against genes expressed only in somatic cells can be abundantly expressed. In contrast, ectopic siRNAs against germline-expressed genes are often suppressed. This phenomenon, which we termed target-directed siRNA suppression, is dependent on the target mRNA and requires germline P-granule components. We found that siRNA suppression can also occur to naturally produced endo-siRNAs. We suggest that siRNA suppression plays an important role in regulating siRNA expression and preventing self-genes from aberrant epigenetic silencing.
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