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Published on: May 1, 2020
The tumor suppressor parafibromin is required for posttranscriptional processing of histone mRNA
Leslie J Farber1, Eric J Kort, PengFei Wang
1Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
Abstract:
Parafibromin, encoded by the gene HRPT2, is a tumor suppressor protein associated with the RNA polymerase II-associated complex, Paf1 complex. HRPT2 mutations were first identified in patients with the multiple endocrine neoplasia syndrome, hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and have also been found in sporadic parathyroid and renal tumors. However, the mechanisms by which parafibromin suppresses tumor formation remain unknown. In this study, we identify a novel role of parafibromin in the regulation of replication-dependent histones. Both in vitro and in vivo analyses reveal a posttranscriptional role of parafibromin in histone mRNA processing. Downregulation of parafibromin through RNA interference or in vivo mutations lead to uncleaved histone mRNA with polyadenylated tails. These results indicate that parafibromin regulates the 3' processing of histone RNA, an essential component of the cell cycle.
Insights
Parafibromin, a tumor suppressor protein, regulates histone mRNA processing. Its downregulation causes uncleaved histone mRNA, impacting the cell cycle and potentially tumor formation.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Parafibromin (HRPT2) is a tumor suppressor protein linked to the Paf1 complex.
- HRPT2 mutations are associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome and sporadic tumors.
- The tumor-suppressive mechanisms of parafibromin are not fully understood.
Purpose of the Study:
- To investigate the role of parafibromin in tumor suppression.
- To elucidate the molecular mechanisms underlying parafibromin's function.
- To identify novel targets regulated by parafibromin.
Main Methods:
- In vitro and in vivo experiments were conducted.
- RNA interference (RNAi) was used to downregulate parafibromin.
- Histone mRNA processing and polyadenylation were analyzed.
Main Results:
- Parafibromin plays a posttranscriptional role in histone mRNA processing.
- Downregulation of parafibromin results in uncleaved histone mRNA with polyadenylated tails.
- This suggests parafibromin is essential for proper 3' end processing of histone RNA.
Conclusions:
- Parafibromin regulates the 3' processing of replication-dependent histone mRNA.
- This function is critical for cell cycle progression.
- Dysregulation of this process may contribute to tumor development.
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