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Current understanding of CREPT and p15RS, carboxy-terminal domain (CTD)-interacting proteins, in human cancers

Oncogene volume 40, pages 705–716 (2021)Cite this article

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Abstract

CREPT and p15RS, also named RPRD1B and RPRD1A, are RPRD (regulation of nuclear pre-mRNA-domain-containing) proteins containing C-terminal domain (CTD)-interacting domain (CID), which mediates the binding to the CTD of Rpb1, the largest subunit of RNA polymerase II (RNAPII). CREPT and p15RS are highly conserved, with a common yeast orthologue Rtt103. Intriguingly, human CREPT and p15RS possess opposite functions in the regulation of cell proliferation and tumorigenesis. While p15RS inhibits cell proliferation, CREPT promotes cell cycle and tumor growth. Aberrant expression of both CREPT and p15RS was found in numerous types of cancers. At the molecular level, both CREPT and p15RS were reported to regulate gene transcription by interacting with RNAPII. However, CREPT also exerts a key function in the processes linked to DNA damage repairs. In this review, we summarized the recent studies regarding the biological roles of CREPT and p15RS, as well as the molecular mechanisms underlying their activities. Fully revealing the mechanisms of CREPT and p15RS functions will not only provide new insights into understanding gene transcription and maintenance of DNA stability in tumors, but also promote new approach development for tumor diagnosis and therapy.

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Fig. 1: A phylogenic tree of the CREPT/p15RS family proteins.
Fig. 2: Sequence alignments of Rtt103, Rhn1, Cids-1, p15RS/RPRD1A, and CREPT/RPRD1B.
Fig. 3: The inhibitory role of p15RS in transcription regulation.
Fig. 4: The models of CREPT in transcription regulation.
Fig. 5: The structures of Rtt103, p15RS, and CREPT.
Fig. 6: The regulation of DNA damage repair by Rtt103 and CREPT.

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Acknowledgements

We thank Dr. Robert N. Eisenman, from Fred Hutchinson Cancer Research Center, for his kindly reading of the manuscript.

Funding

This work was supported by grants from the Chinese National Major Scientific Research Program (2016YFA0500301), and grants from the National Natural Science Foundation of China (81830092, 81230044).

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  1. State Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, 100084, Beijing, China

    Mengdi Li, Danhui Ma & Zhijie Chang

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Li, M., Ma, D. & Chang, Z. Current understanding of CREPT and p15RS, carboxy-terminal domain (CTD)-interacting proteins, in human cancers. Oncogene 40, 705–716 (2021). https://doi.org/10.1038/s41388-020-01544-0

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