Expression of RNA polymerase I catalytic core is influenced by RPA12.
RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA13...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0285660 |
| _version_ | 1827292688149381120 |
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| author | Brittany L Ford Ting Wei Hester Liu Catherine E Scull Saman M Najmi Stephanie Pitts Wenjun Fan David A Schneider Marikki Laiho |
| author_facet | Brittany L Ford Ting Wei Hester Liu Catherine E Scull Saman M Najmi Stephanie Pitts Wenjun Fan David A Schneider Marikki Laiho |
| author_sort | Brittany L Ford |
| collection | DOAJ |
| description | RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA135, and RPA12, a subunit with functions in RNA cleavage, transcription initiation and elongation. Here we explore whether RPA12 influences the regulation of RPA194 in human cancer cells. We use a specific small-molecule Pol I inhibitor BMH-21 that inhibits transcription initiation, elongation and ultimately activates the degradation of Pol I catalytic subunit RPA194. We show that silencing RPA12 causes alterations in the expression and localization of Pol I subunits RPA194 and RPA135. Furthermore, we find that despite these alterations not only does the Pol I core complex between RPA194 and RPA135 remain intact upon RPA12 knockdown, but the transcription of Pol I and its engagement with chromatin remain unaffected. The BMH-21-mediated degradation of RPA194 was independent of RPA12 suggesting that RPA12 affects the basal expression, but not the drug-inducible turnover of RPA194. These studies add to knowledge defining regulatory factors for the expression of this Pol I catalytic subunit. |
| first_indexed | 2024-03-13T05:00:09Z |
| format | Article |
| id | doaj.art-deb9e959af1549c0995c621a11a4bf5f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-24T13:09:01Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-deb9e959af1549c0995c621a11a4bf5f2024-04-05T05:33:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185e028566010.1371/journal.pone.0285660Expression of RNA polymerase I catalytic core is influenced by RPA12.Brittany L FordTing WeiHester LiuCatherine E ScullSaman M NajmiStephanie PittsWenjun FanDavid A SchneiderMarikki LaihoRNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA135, and RPA12, a subunit with functions in RNA cleavage, transcription initiation and elongation. Here we explore whether RPA12 influences the regulation of RPA194 in human cancer cells. We use a specific small-molecule Pol I inhibitor BMH-21 that inhibits transcription initiation, elongation and ultimately activates the degradation of Pol I catalytic subunit RPA194. We show that silencing RPA12 causes alterations in the expression and localization of Pol I subunits RPA194 and RPA135. Furthermore, we find that despite these alterations not only does the Pol I core complex between RPA194 and RPA135 remain intact upon RPA12 knockdown, but the transcription of Pol I and its engagement with chromatin remain unaffected. The BMH-21-mediated degradation of RPA194 was independent of RPA12 suggesting that RPA12 affects the basal expression, but not the drug-inducible turnover of RPA194. These studies add to knowledge defining regulatory factors for the expression of this Pol I catalytic subunit.https://doi.org/10.1371/journal.pone.0285660 |
| spellingShingle | Brittany L Ford Ting Wei Hester Liu Catherine E Scull Saman M Najmi Stephanie Pitts Wenjun Fan David A Schneider Marikki Laiho Expression of RNA polymerase I catalytic core is influenced by RPA12. PLoS ONE |
| title | Expression of RNA polymerase I catalytic core is influenced by RPA12. |
| title_full | Expression of RNA polymerase I catalytic core is influenced by RPA12. |
| title_fullStr | Expression of RNA polymerase I catalytic core is influenced by RPA12. |
| title_full_unstemmed | Expression of RNA polymerase I catalytic core is influenced by RPA12. |
| title_short | Expression of RNA polymerase I catalytic core is influenced by RPA12. |
| title_sort | expression of rna polymerase i catalytic core is influenced by rpa12 |
| url | https://doi.org/10.1371/journal.pone.0285660 |
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