# POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION

> **NIH NIH R01** · PRINCETON UNIVERSITY · 1992 · $119,089

## Abstract

Adenovirus-infected cells provide an ideal opportunity to investigate
post-transcriptional regulation of gene expression:  during the late
phase of infection, cellular gene expression is completely inhibited as
a result of selective transport of mature, viral mRNA species form the
nucleus to the cytoplasm and selective translation of cytoplasmic, viral
mRNA mRNAs.  The experiments described in this proposal are designed to
provide a better understanding of the mechanisms whereby such post-
transcriptional discrimination among mRNA species is mediated and thus
improve our knowledge not only of the repertoire of regulatory circuits
that operate in eukaryotic cells, but also of the ways in which virus
infection can disrupt cellular metabolism.

The roles of such parameters as location in the viral genome, activation
of transcription and specific signals carried by viral mRNA in selection
of mRNA species for transport form adenovirus-infected cell nuclei to
the cytoplasm will be investigated, using both a series of non-
adenoviral genes expressed from sites within the viral genome, the
cellular genome or from episomal plasmids, and mutated, viral, late
genes.  In each case, all steps in production of mRNA species from such
genes, as well as cytoplasmic mRNA stability, will be examined during
adenovirus infection so that the effects of such parameters on the
transport step itself can be assessed. The viral E1B 55kd and E4 early
proteins have been implicated in selective transport of mRNA during the
late phase of productive infection.  Viruses carrying mutations in these
coding sequences will therefore be used to investigate the role of these
protein in recognition of any parameter that appear essential to
selective transport.  We have recently established, by screening of
temperature-sensitive adenovirus mutants, that the late, non-structural
100kd protein plays an important role in efficient translation of viral,
late mRNA species, by a mechanism that appears to operate at the level
of initiation of translation.  This molecular function of the 100kd
protein will be investigated in more detail, both by analysis of the
interactions of this protei with mRNA and translational components, and
by establishment of in vitro system in which its translational function
is reproduced.

## Key facts

- **NIH application ID:** 3127082
- **Project number:** 5R01AI017265-12
- **Recipient organization:** PRINCETON UNIVERSITY
- **SAM.gov UEI:** NJ1YPQXQG7U5
- **Principal Investigator:** Sarah Jane FLINT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $119,089
- **Award type:** 5
- **Project period:** 1980-08-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127082

## Citation

> US National Institutes of Health, RePORTER application 3127082, POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION (5R01AI017265-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127082. Licensed CC0.

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