# REGULATION OF MRNA TURNOVER IN DIFFERENTIATING LEUKEMIA

> **NIH NIH R01** · BOSTON BIOMEDICAL RESEARCH INSTITUTE · 1987 · $185,612

## Abstract

This proposal will focus on two aspects of mRNA turnover in differentiating
leukemia cells.  The first concerns changes in mRNA stability and their
possible relationship to changes in mRNA structure and involves the
comparison of complementary DNAs in noninduced and differentiating leukemia
cells.  The second concerns a novel mechanism for mRNA synthesis which may
play an important role in terminal differentiation and involves an
RNA-dependent RNA polymerase.  We observed this activity while studying the
metabolism of mRNA in differentiating murine erythroleukemia cells.  The
kinetics of globin mRNA synthesis in these cells, its subcellular
localization, size, distribution among different RNA fractions, and drug
sensitivity can be most easily explained by postulating cytoplasmic
RNA-dependent RNA synthesis.  Our discovery of "minus" globin RNA strand in
differentiating MEL cells supports this conclusion.  The present proposal
will focus on three aspects of RNA-dependent RNA synthesis in murine
erythroleukemia cells.  The first deals with the purification and
characterization of the protein components required for RNA-dependent RNA
synthesis and with the question whether essential components may have
general cellular function besides their involvement in erythropoetic
differentiation.  The second involves a detailed study of the mechanism of
RNA-dependent RNA synthesis, including the mechanism of initiation of
minus-strand synthesis, of RNA chain elongation, of synthesis of the
positive strand from a minus-strand template, and the factors involved in
template recognition.  Most of these studies will be carried out with
purified components, but parallel investigations will utilize an in vivo
system consisting of enucleated cells that have been selectively
permeabilized to precursors of macromolecular synthesis.  The third aspect
concerns the biological significance of RNA-dependent RNA synthesis and
addresses itself to the questions whether this process is unique to
erythropoetic differentiation or plays a role in other types of
differentiation or perhaps even in all eucaryotic cells and whether it
applies to the amplification of only certain types of mRNA or to all mRNA
species.

## Key facts

- **NIH application ID:** 3171709
- **Project number:** 5R01CA033953-05
- **Recipient organization:** BOSTON BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** VLADIMIR Z VOLLOCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $185,612
- **Award type:** 5
- **Project period:** 1983-01-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171709

## Citation

> US National Institutes of Health, RePORTER application 3171709, REGULATION OF MRNA TURNOVER IN DIFFERENTIATING LEUKEMIA (5R01CA033953-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171709. Licensed CC0.

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