TY - JOUR
T1 - The cancer testis antigen TDRD1 regulates prostate cancer proliferation by associating with the snRNP biogenesis machinery
AU - Kim, Hong
AU - Barua, Amrita
AU - Huang, Luping
AU - Zhou, Tianyi
AU - Bolaji, Modupeola
AU - Zachariah, Sharon
AU - Mitra, Aroshi
AU - Jung, Sung Yun
AU - He, Bin
AU - Feng, Qin
N1 - Funding Information:
This work was supported by the NIH (R01CA211861 to BH, R33AI122418 and R33AI133697 to QF, and S10OD026827-01A1 to BBIC core at the University of Houston).
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/6/2
Y1 - 2023/6/2
N2 - Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-specific gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identified a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the final snRNP assembly takes place in Cajal bodies in the nucleus. By mass spectrum analysis, we found that TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 interacts with methylated Sm proteins in a PRMT5-dependent manner. In the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 in prostate cancer cells disrupted the integrity of Cajal bodies, affected the snRNP biogenesis, and reduced cell proliferation. Taken together, this study represents the first characterization of TDRD1 functions in prostate cancer development and suggests TDRD1 as a potential therapeutic target for prostate cancer treatment.
AB - Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-specific gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identified a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the final snRNP assembly takes place in Cajal bodies in the nucleus. By mass spectrum analysis, we found that TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 interacts with methylated Sm proteins in a PRMT5-dependent manner. In the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 in prostate cancer cells disrupted the integrity of Cajal bodies, affected the snRNP biogenesis, and reduced cell proliferation. Taken together, this study represents the first characterization of TDRD1 functions in prostate cancer development and suggests TDRD1 as a potential therapeutic target for prostate cancer treatment.
KW - Male
KW - Humans
KW - Ribonucleoproteins, Small Nuclear/genetics
KW - Testis/metabolism
KW - Cell Nucleus/metabolism
KW - Prostatic Neoplasms/genetics
KW - Cell Proliferation/genetics
KW - HeLa Cells
KW - Protein-Arginine N-Methyltransferases/genetics
KW - Cell Cycle Proteins/metabolism
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U2 - 10.1038/s41388-023-02690-x
DO - 10.1038/s41388-023-02690-x
M3 - Article
C2 - 37041411
AN - SCOPUS:85152411351
SN - 0950-9232
VL - 42
SP - 1821
EP - 1831
JO - Oncogene
JF - Oncogene
IS - 22
ER -