TY - JOUR
T1 - A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
AU - Van Bortle, Kevin
AU - Marciano, David P.
AU - Liu, Qing
AU - Chou, Tristan
AU - Lipchik, Andrew M.
AU - Gollapudi, Sanjay
AU - Geller, Benjamin S.
AU - Monte, Emma
AU - Kamakaka, Rohinton T.
AU - Snyder, Michael P.
N1 - We thank Dr. Joshua J. Gruber, Dr. E. Peter Geiduschek, Dr. Suhas Rao, Dr. Eric Phizicky, Dr. Howard Chang, Dr. Rebecca Harper, and members of the Snyder lab and Kornberg lab for insightful discussion and feedback. We thank Lucia Ramirez, Ada Chen, Lisa Stainton, and Maria Manzanilla-Owen for logistical support. Illumina sequencing services were performed by the Genome Sequencing Service Center by Stanford Center for Genomics and Personalized Medicine Sequencing Center. The results in this study are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga K.V.B is supported by National Institutes of Health, National Human Genome Research Institute (NHGRI) grant R00HG010362. D.P.M. is support by National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) grant K99HL145097. Q.L. is supported by American Heart Associated Career Development Award 18CDA34110128. R.T.K. was supported by GM078068. This research was supported by NIH Centers of Excellence in Genomic Science (CEGS) grant 5P50HG00773502. This work used the Genome Sequencing Service Center by Stanford Center for Genomics and Personalized Medicine Sequencing Center, supported by NIH grant award S10OD020141.
PY - 2022/12
Y1 - 2022/12
N2 - RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions of POLR3G and POLR3GL to transcription potential has remained poorly defined. Here, we discover that loss of subunit POLR3G is accompanied by a restricted repertoire of genes transcribed by Pol III. Particularly sensitive is snaR-A, a small noncoding RNA implicated in cancer proliferation and metastasis. Analysis of Pol III isoform biases and downstream chromatin features identifies loss of POLR3G and snaR-A during differentiation, and conversely, re-establishment of POLR3G gene expression and SNAR-A gene features in cancer contexts. Our results support a model in which Pol III identity functions as an important transcriptional regulatory mechanism. Upregulation of POLR3G, which is driven by MYC, identifies a subgroup of patients with unfavorable survival outcomes in specific cancers, further implicating the POLR3G-enhanced transcription repertoire as a potential disease factor.
AB - RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions of POLR3G and POLR3GL to transcription potential has remained poorly defined. Here, we discover that loss of subunit POLR3G is accompanied by a restricted repertoire of genes transcribed by Pol III. Particularly sensitive is snaR-A, a small noncoding RNA implicated in cancer proliferation and metastasis. Analysis of Pol III isoform biases and downstream chromatin features identifies loss of POLR3G and snaR-A during differentiation, and conversely, re-establishment of POLR3G gene expression and SNAR-A gene features in cancer contexts. Our results support a model in which Pol III identity functions as an important transcriptional regulatory mechanism. Upregulation of POLR3G, which is driven by MYC, identifies a subgroup of patients with unfavorable survival outcomes in specific cancers, further implicating the POLR3G-enhanced transcription repertoire as a potential disease factor.
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U2 - 10.1038/s41467-022-30323-6
DO - 10.1038/s41467-022-30323-6
M3 - Article
C2 - 35637192
AN - SCOPUS:85130893761
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3007
ER -