Alu element‐containing RNA s maintain nucleolar structure and function

Abstract

Non‐coding RNA s play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep‐sequencing‐based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements ( alu RNA s) were enriched in the nucleolus. Antisense‐oligo‐mediated depletion of alu RNA s or drug‐induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I‐dependent transcription of rRNA genes. In contrast, overexpression of a prototypic alu RNA sequence increased both nucleolus size and levels of pre‐ rRNA , suggesting a functional link between alu RNA , nucleolus integrity and pre‐ rRNA synthesis. Furthermore, we show that alu RNA s interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an alu RNA ‐based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production. image The human genome encodes thousands of Alu repeats of unclear function. This study shows intronic Alu elements transcribed by RNA Pol II to be enriched in the nucleolus where they maintain nucleolar integrity and ensure pre‐ rRNA synthesis. Intronic Alu element‐containing RNA s ( alu RNA s) are enriched in the nucleolus. Depletion of alu RNA s disrupts nucleolar structure and impairs rRNA production, while overexpression of alu RNA s increases both nucleolus size and rRNA levels. alu RNA s interact with nucleolin and can target large genomic loci to the nucleolus. alu RNA s are produced by RNA polymerase II and link its activity to rRNA production by RNA polymerase I.