PIWI-interacting RNAs (piRNAs), a class of conserved non-coding small RNAs, are essential for sex determination, defense against viruses, and maintaining genome integrity of diverse animal species. The missing of PIWI protein would lead to male-production of sperm. However, many piRNA clusters reside within or close to the heterochromatin, a transcriptional silencing loci. How piRNAs are transcribed remains unknown.

In a study published in PNAS on July 6, Prof. GUANG Shouhong and FENG Xuezhu from University of Science and Technology  identified a chromodomain-containing protein, UAD-2, in the model organism Caenorhabditis elegans (C. elegans), and determined the role of UAD-2 in the regulation of gene transcription in heterochromatin regions.

In 2019, Prof. GUANG and the international collaborators discovered the upstream sequence transcription complex (USTC) and specified its role in the biogenesis process of piRNAs (Genes & Development). Using the USTC complex as a tool, the researchers in this study isolated a USTC association-dependent mutant, or uad-2 for short, in which the piRNA foci were depleted, by clonal screening.

Subsequent experiments confirmed that the uad-2 genome was essential for the genesis of piRNAs.

A working model of UAD-2–directed piRNA expression. (Image by HUANG Xinya et al.)

In addition, the researchers found that the UAD-2 protein and the USTC complex colocalized with each other in the nucleus, and they were mutually dependent on each other for the proper localization. Thus, the UAD-2 was required in the production of piRNAs by this mutual effect with the USTC complex.

Many piRNA loci overlap with a heterochromatin mark histone called H3K27me3 in C. elegans. The chromodomain in the UAD-2 is one of the major readers of the histone mark, and exogenous experiments proved that the H3K27me3 promoted UAD-2 and USTC focus assembly. Proper modification of H3K27me3 was also important to the generation of piRNAs.

The findings of this study provide a new way to study the transcription of piRNA in heterochromatin region.

Paper link: https://www.pnas.org/content/118/27/e2103723118

(Written by JIANG Pengcen, edited by HOU Luyao, USTC News Center)