Academic journal article Genetics

Communication between Parental and Developing Genomes during Tetrahymena Nuclear Differentiation Is Likely Mediated by Homologous RNAs

Academic journal article Genetics

Communication between Parental and Developing Genomes during Tetrahymena Nuclear Differentiation Is Likely Mediated by Homologous RNAs

Article excerpt

ABSTRACT

Approximately 6000 DNA elements, totaling nearly 15 Mb, are coordinately excised from the developing somatic genome of Tetrahymena thermophila. An RNA interference (RNAi)-related mechanism has been implicated in the targeting of these germline-limited sequences for chromatin modification and subsequent DNA rearrangement. The excision of individual DNA segments can be inhibited if the homologous sequence is placed within the parental somatic nucleus, indicating that communication occurs between the parental and developing genomes. To determine how the DNA content of one nucleus is communicated to the other, we assessed DNA rearrangement occurring in wild-type cells that were mated to cells that contained the normally germline-limited M element within their somatic nuclei. M-element rearrangement was blocked in the wild-type cell even when no genetic exchange occurred between mating partners, a finding that is inconsistent with any genetic imprinting models. This inhibition by the parental somatic nucleus was rapidly established between 5 and 6 hr of conjugation, near or shortly after the time that zygotic nuclei are formed. M-element small RNAs (sRNAs) that are believed to direct its rearrangement were found to rapidly accumulate during the first few hours of conjugation before stabilizing to a low, steady-state level. The period between 5 and 6 hr during which sRNA levels stabilize correlates with the time after which the parental genome can block DNA rearrangement. These data lead us to suggest that homologous sRNAs serve as mediators to communicate sequence-specific information between the parental and developing genomes, thereby regulating genome-wide DNA rearrangement, and that these sRNAs can be effectively compared to the somatic genome of both parents.

EUKARYOTIC cells go to great lengths to ensure the integrity of their genomes. In addition to mechanisms that orchestrate the sequential events of chromosome replication and division, others exist that protect the genome from the spread of invading DNA elements. The existence of such genome defense mechanisms has been uncovered largely due to studies of diverse epigenetic phenomena such as transgene-induced silencing or cosuppression, described in both plants and animals (see WATERHOUSE et al. 2001), and repeat-induced point mutation or gene silencing in fungi (GOYON and FAUGERON 1989; SELKER 1990, 2002).

Studies from the last several years have revealed that the triggers for many such homology-dependent events are likely double-stranded RNAs (dsRNAs; reviewed in HANNON 2002). The epigenetic phenomena induced by dsRNA have been collectively called RNA interference (RNAi)-related processes. The dsRNA molecules are processed into 20-30 nucleotide effector species by an RNAse III-related protein called Dicer (BERNSTEIN et al. 2001). Mutations in genes required for RNAi in Caenorhabditis elegans result in the mobilization of transposable elements, providing further evidence that RNAi appears to serve as a genome defense mechanism that silences invading DNA elements to limit their spread to other loci (KETTING et al. 1999; TABARA et al. 1999). Furthermore, the RNAi machinery of Schizosaccharomyces pombe is required for heterochromatin formation at the matingtype locus and for silencing of centromeric repeats (HALL et al. 2002; VOLPE et al. 2002), which implicates this process in endogenous mechanisms important for chromosome stability (see DERNBURG and KARPEN 2002).

The ciliated protozoan Tetrahymena thermophila has emerged as a useful model to understand how eukaryotic cells can differentially regulate individual copies of homologous sequence. Tetrahymena, like other ciliated protozoa, are unusual in that these single-celled organisms contain two functionally distinct genomes, which serve the equivalent of germline and somatic roles (reviewed in KARRER 2000). The germline genome is contained within the transcriptionally silent micronucleus that primarily serves as the genetic repository to pass along an intact genome during sexual development. …

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