Biology subjects

Zamore, P.

Publications and source records attributed to Zamore, P..

2 recordsLinked to original sources

bioRxiv2018

Maelstrom Represses Canonical Polymerase II Transcription within Bi-Directional piRNA Clusters in Drosophila melanogaster

In Drosophila, 23-30 nt long PIWI-interacting RNAs (piRNAs) direct the protein Piwi to silence germline transposon transcription. Most germline piRNAs derive from dual-strand piRNA clusters, heterochromatic transposon graveyards that are transcribed from both genomic strands. These piRNA sources are marked by the Heterochromatin Protein 1 homolog, Rhino (Rhi), which facilitates their promoter-independent transcription, suppresses splicing, and inhibits transcriptional termination. Here, we report that the protein Maelstrom (Mael) represses canonical, promoter-dependent transcription in dual-strand clusters, allowing Rhi to initiate piRNA precursor transcription. In addition to Mael, the piRNA biogenesis factors Armitage and Piwi, but not Rhi, are required to repress canonical transcription in dual-strand clusters. We propose that Armitage, Piwi, and Mael collaborate to repress potentially dangerous transcription of individual transposon mRNAs within clusters, while Rhi allows non-canonical transcription of the clusters into piRNA precursors without generating transposase-encoding mRNAs.

genetics↗

bioRxiv2018

PIWI Proteins Act at Multiple Steps in the Production of Their Own Guides

In animals, piRNAs guide PIWI-proteins to silence transposons and regulate gene expression. The mechanisms for making piRNAs have been proposed to differ among cell types, tissues, and animals. Our data instead suggest a single model that explains piRNA production in most animals. piRNAs initiate piRNA production by guiding PIWI proteins to slice precursor transcripts. Next, PIWI proteins direct the stepwise fragmentation of the sliced precursor transcripts, yielding tail-to-head strings of phased pre-piRNAs. Our analyses detect evidence for this piRNA biogenesis strategy across an evolutionarily broad range of animals including humans. Thus, PIWI proteins initiate and sustain piRNA biogenesis by the same mechanism in species whose last common ancestor predates the branching of most animal lineages. The unified model places PIWI-clade Argonautes at the center of piRNA biology and suggests that the ancestral animal--the Urmetazoan--used PIWI proteins both to generate piRNA guides and to execute piRNA function.

molecular biology↗