Poster abstracts
Poster number 30 submitted by Jenny Ruiying Cheng
The NuRD chromatin remodeler as a novel regulator of RNA polymerase III and the small RNA universe
Ruiying Cheng (University of Illinois Urbana-Champaign), Rajendra K C (University of Illinois Urbana-Champaign), Sihang Zhou (University of Illinois Urbana-Champaign), Simon Lizarazo (University of Illinois Urbana-Champaign), Kevin Van Bortle (University of Illinois Urbana-Champaign)
Abstract:
RNA polymerase (Pol) III is centrally involved in shaping the small RNA universe, producing diverse noncoding RNAs (ncRNA) such as tRNA, 5S rRNA, and U6 small nuclear RNA (snRNA) integral for translation, RNA processing, and other processes critical for cell growth. However, despite being a major determinant of small RNA abundance in a cell, Pol III transcription and the mechanisms mediating its dynamic and tissue-specific activities remain unresolved. To address this gap, we used an unbiased proteomic approach to identify Pol III protein-protein interactions and thereby predict novel regulators of Pol III transcription. Notably, we discover 14 out of 15 NuRD (Nucleosome Remodeling and Deacetylase) complex subunits in our survey, which together mediate histone deacetylation and ATP-dependent chromatin remodeling. We therefore further explored the global landscape of NuRD occupancy using an innovative large-scale genomic approach that combines all available NuRD-binding data in humans. Our genomic survey identifies widespread NuRD occupancy at most Pol III-transcribed gene classes, further supporting NuRD as a putative Pol III regulator. Finally, we test this hypothesis using a combination of small molecule inhibition and other functional genomic methods to investigate the contribution of NuRD activity on Pol III transcription. Our preliminary data suggest the NuRD complex’s histone deacetylation activity negatively regulates Pol III transcription, consistent with its established role in regulating non-Pol III transcribed genes. Taken together, our study points to the NuRD chromatin remodeling complex as a novel modulator of Pol III transcription with important implications for the small RNA universe.
Keywords: Expression Regulation, Small Non-Coding RNA, RNA Polymerase III