PLOS Genetics study identifies HNRNPU as a required factor in long-range Polycomb silencing by imprinting lncRNAs

A study published in PLOS Genetics by McKenzie M. Murvin, Shuang Li, and colleagues at the University of North Carolina Chapel Hill reports new mechanistic detail on how two imprinted long non-coding RNAs (lncRNAs), Airn and Kcnq1ot1, recruit Polycomb Repressive Complexes (PRCs) to silence genes across multi-megabase genomic intervals in mouse trophoblast stem cells.

Using formaldehyde-linked RNA immunoprecipitation (RIP) of 27 proteins, the team generated a correlated map of protein–RNA associations for both lncRNAs. The data revealed that, despite the two lncRNAs operating at different imprinted loci and sharing limited sequence similarity, their protein-interaction landscapes show notable parallels. Critically, the study identifies the RNA-binding protein HNRNPU as specifically required for the long-range recruitment of PRCs by both Airn and Kcnq1ot1: loss of HNRNPU disrupts silencing across distal portions of the repressed domains without abolishing PRC association at proximal regions.

The findings contribute to understanding of how lncRNAs achieve chromosomal-scale gene regulation — a question relevant to genomic imprinting, dosage compensation, and the broader biology of non-coding RNA in development. The mechanisms described here operate in mouse trophoblast cells; their relevance to human imprinting loci will require direct investigation.

The paper is published as an open-access article in PLOS Genetics.