Small RNAs as guardians of the genome - PubMed (original) (raw)

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Small RNAs as guardians of the genome

Colin D Malone et al. Cell. 2009.

Abstract

Transposons populate the landscape of all eukaryotic genomes. Often considered purely genomic parasites, transposons can also benefit their hosts, playing roles in gene regulation and in genome organization and evolution. Peaceful coexistence with mobile elements depends upon adaptive control mechanisms, since unchecked transposon activity can impact long-term fitness and acutely reduce the fertility of progeny. Here, we review the conserved roles played by small RNAs in the adaptation of eukaryotes to coexist with their genomic colonists. An understanding of transposon-defense pathways has uncovered recurring themes in the mechanisms by which genomes distinguish "self" from "non-self" and selectively silence the latter.

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Figures

Figure 1

Figure 1. Strategies for Shaping Small RNA Populations

Ping-pong and RNA-dependent RNA polymerase (RDRP) cycles amplify small RNA populations against target molecules. (A) Maternal, and possibly primary, cluster-derived piRNAs initiate the ping-pong cycle by targeting the cleavage of transposon transcripts. A secondary piRNA is then produced after a 3′ cleavage of unknown source. AGO3 loads secondary piRNAs, which then target the cleavage of antisense transposon transcripts from piRNA clusters. A novel piRNA is subsequently produced and loaded into Aub, which can then target an additional transposon transcript, restarting the amplification cycle. (TGS, transcriptional gene silencing.) (B) Transcripts targeted by small RNAs are cleaved by the RNA-induced silencing complex (RISC). RDRP subsequently loads and reverse-transcribes the transcript. The new dsRNA molecule is recognized and processed into small RNAs by a Dicer protein, followed by loading of single-stranded small RNAs into RISC. Finally, RISC is able to target additional cellular transcripts and restart the cycle.

Figure 2

Figure 2. Model of RNAi-Based Scanning and Sequence Elimination in Tetrahymena thermophila

Simplified view of Twi1p scanning and targeting of sequence elimination. Nuclear development is not depicted (see Matzke and Birchler, 2005, for a detailed overview of nuclear progression during development). Each depicted cell is one of a mating pair (shaded cells). (A) Generation of scan RNAs (scnRNAs) from the eliminated (green) and noneliminated (orange) germline sequences. (B) Micronuclear export and loading of scnRNAs into cytoplasmic Twi1p. (C) Twi1p import into the parental macronucleus, where Twi1p with bound scnRNAs “scans” the parental genome and are depleted from the population if matching to the parental, rearranged genome. (D) Export of Twi1p, bound with eliminated-element-enriched scnRNAs, to the cytoplasm. (E) Twi1p import into the developing macronucleus followed by targeting of elements to be eliminated with histone modifications (me, methylation). (F) The newly rearranged macronuclear genome after recognition and elimination of elements targeted by the rearrangement machinery.

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