The USTC co-opts an ancient machinery to drive piRNA transcription in C. elegans.

Chenchun Weng,Yong-Hong Yan,Xuezhu Feng,Wen-Jun Li,Orsolya Barabas,Przemyslaw Stempor,Shouhong Guang,Natalia Rosalía Morero,Ahmet C Berkyurek,Meng-Qiu Dong,Joanna Kosalka,Chenming Zeng,Cecilia Zuliani,Eric A Miska,Julie Ahringer,Hui Mao

doi:10.1101/gad.319293.118

Abstract

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. In Caenorhabditis elegans, most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis, the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC contains piRNA silencing-defective 1 (PRDE-1), SNPC-4, twenty-one-U fouled-up 4 (TOFU-4), and TOFU-5. The USTC forms unique piRNA foci in germline nuclei and coats the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and forming the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other noncoding RNA genes. These results reveal the USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defense against transposons.

Highlights

Piwi-interacting RNAs engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms
It was found that a small nuclear RNAactivating complex protein, SNPC-4, colocalize with piRNA silencing-defective 1 (PRDE-1) and promotes Piwi-interacting RNAs (piRNAs) biogenesis (Kasper et al 2014)
By a series of proteomics, imaging, and ChIP-seq experiments, we demonstrate that the four proteins PRDE-1, SNPC-4, twenty-one-U fouled-up 4 (TOFU-4), and twenty-one-U fouled-ups (TOFUs)-5 function as a complex and bind to the promoter sequences of individual piRNA transcription units

Summary

Introduction

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. USTC components bind differentially to piRNAs in the clusters and other noncoding RNA genes These results reveal the USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defense against transposons. In Caenorhabditis elegans, piRNAs preserve genome integrity in the germline by recognizing and silencing “nonself” genomic loci such as transposons or other foreign nucleic acids and induce chromatin modifications (Malone and Hannon 2009; Ashe et al 2012; Bagijn et al 2012; Feng and Guang 2013; Luteijn and Ketting 2013; Mao et al 2015). The mouse piRNAs are classified into prepachytene and pachytene piRNAs based on their expression patterns (Aravin et al 2008; Li et al 2013)—pachytene piRNA transcription distinctively requiring the transcription factor A-MYB (Li et al 2013)

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