PT  - JOURNAL ARTICLE
AU  - Xiangduo Kong
AU  - Yen-Yun Chen
AU  - Jianhuang Lin
AU  - Ebony Flowers
AU  - Eric Van Nostrand
AU  - Steven M. Blue
AU  - Jonathan Chau
AU  - Christopher I-Hsing Ma
AU  - Isaiah Mohr
AU  - Ryan Thai
AU  - Chengguo Yao
AU  - Alexander R. Ball, Jr.
AU  - Richard Chien
AU  - Shimako Kawauchi
AU  - Rosalyn Santos
AU  - Anne L. Calof
AU  - Arthur D. Lander
AU  - Yongsheng Shi
AU  - Mitsuru Okuwaki
AU  - Gene W. Yeo
AU  - Kyoko Yokomori
TI  - The cohesin loader NIPBL interacts with pre-ribosomal RNA and treacle to regulate ribosomal RNA synthesis
AID  - 10.1101/658492
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 658492
4099  - http://biorxiv.org/content/early/2019/06/03/658492.short
4100  - http://biorxiv.org/content/early/2019/06/03/658492.full
AB  - NIPBL is an essential loader of cohesin to mediate sister chromatid cohesion and chromatin loop organization. NIPBL mutations cause Cornelia de Lange Syndrome. How NIPBL’s genomic localization is specified is not fully understood. We found that NIPBL localizes to the nucleolus in an RNA-dependent manner and binds directly to ribosomal RNA (rRNA). We identified two RNA binding domains in NIPBL in vitro, both of which are required for efficient rRNA binding in vivo. NIPBL binds to ribosomal DNA (rDNA) in an RNA-stimulated manner, recruits PAF1 and promotes pre-rRNA transcription. Stress that inhibits rRNA synthesis displaces NIPBL from the nucleolus and rDNA. Interestingly, treacle, mutated in Treacher Collins syndrome, tightly binds to and recruits NIPBL to the nucleolus, nucleolar organizer regions, and the stress-induced nucleolar cap. The results reveal that a subpopulation of NIPBL is recruited to the nucleolus through its interaction with RNA and treacle and regulates pre-rRNA transcription.