# CONTROL OF RRNA SYNTHESIS BY CARCINOGENS AND HORMONES

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 1988 · $157,248

## Abstract

The specificity of the anti-RNA polymerase I antibodies raised in rabbits
was further confirmed by microinjection of purified IgG into the nuclei of
quiescent Swiss 3T3 cells that were subsequently stimulated with serum (in
collaboration with Dr. Renato Baserga).  The microinjected immune
IgG-inhibited nucleolar RNA synthesis (as measured by decrease in the
number of grains derived from [-3H] uridine) decreased by 50 to 70%
which persisted for at least 17 hrs.  Preimmune IgG had no effect on the
nucleolar RNA synthesis.  Under these conditions, nucleoplasmic RNA
synthesis was not altered.  A 70% decrease in the content of nucleolar RNA
was also observed following microinjection of antibodies directed against
RNA polymerase I.

Previous studies in this laboratory have shown that highly purified RNA
polymerase I from rat hepatoma contains protein kinase activity which can
phosphorylate and consequently activate the polymerase.  In every respect,
this kinase resembles nuclear protein kinase NII which consists of two
subunits of Mr = 42,000 and 25,000.  The possibility that two of the RNA
polymerase I subunits of Mr = 42,000 and 25,000 might correspond to the
protein kinase NII has been raised.  Subsequent studies have shown that
sera from patients with certain rheumatic autoimmune diseases contains
antibodies to RNA polymerase I and that each patient exhibits a distinct
spectrum of antibodies to spoecific subunits of the enzyme.  Sera
containing antibodies to subunits of Mr = 42,000and 25,000 always had
antibodies to protein kinase NII, which suggests a biological association
between the two enzymes.  To determine whether protein kinase NII plays a
role in the accurate transcription of rDNA, transcription of cloned rat
rDNA containing the promoter and the initiation site was investigated
using a partially purified whole cell extract.  Fraction eluting at 175 mM
(NH4)2SO4 from DEAE-Sephadex column was resolved into two fractions
using heparin-sepharose column; one eluting with 0.2 M NH4Cl (A) and the
other eluting with 1 M NH4Cl (B) which contains RNA polymerase I
activity.  Either fraction A or B by itself did not support accurate
transcription, but reconstitution of the two fractions yielded the
anticipated transcript. More recent studies have shown that under certain
conditions a transcriptionally active fraction containing RNA polymerase I
and protein kinase NII can be obtained upon heparin sepharose
chromatography.  We are now in a position to dissociate this complex and
determine the exact role of the protein kinase in rDNA transcription.  (G)

## Key facts

- **NIH application ID:** 3170007
- **Project number:** 5R01CA031894-07
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **SAM.gov UEI:** TNKGNDAWB445
- **Principal Investigator:** SAMSON T JACOB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $157,248
- **Award type:** 5
- **Project period:** 1982-07-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170007

## Citation

> US National Institutes of Health, RePORTER application 3170007, CONTROL OF RRNA SYNTHESIS BY CARCINOGENS AND HORMONES (5R01CA031894-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170007. Licensed CC0.

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