4.8 Article

A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA

期刊

NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -

出版社

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-30323-6

关键词

-

资金

  1. National Institutes of Health, National Human Genome Research Institute (NHGRI) [R00HG010362]
  2. National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) [K99HL145097]
  3. American Heart Associated Career Development Award [18CDA34110128]
  4. NIH Centers of Excellence in Genomic Science (CEGS) [5P50HG00773502]
  5. NIH [S10OD020141]
  6. [GM078068]

向作者/读者索取更多资源

This study reveals that loss of subunit POLR3G in RNA polymerase III (Pol III) leads to a restricted repertoire of transcribed genes, particularly affecting the transcription of snaR-A, a noncoding RNA associated with cancer proliferation and metastasis. The findings suggest that Pol III identity plays an important role in transcriptional regulation. Upregulation of POLR3G, driven by MYC, is associated with unfavorable survival outcomes in certain cancers.
RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7 alpha) or POLR3GL (RPC7 beta), 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. RNA polymerase III changes its subunit composition during mammalian development. Here the authors report that loss of subunit POLR3G, which re-emerges in cancer, promotes expression of small NF90-associated RNA (snaR-A), a noncoding RNA implicated in cell proliferation and metastasis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据