# RACK1-mediated control of mRNA selectivity by poxviruses

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2020 · $45,520

## Abstract

ABSTRACT
Viruses have evolved mechanisms to use 5’ untranslated regions (UTRs) to control viral protein synthesis during
infection. For example, many RNA viruses use internal ribosome entry sites in the 5’ UTRs. By contrast,
poxviruses, such as Vaccinia virus, encode polyadenosine (polyA) repeats in the 5’ UTR of post-replicative
mRNA that enhance the translation of poxviral transcripts. The functionality of the polyA enhancer effect in
human cells is dependent on poxvirus-mediated phosphorylation of an extended loop of the small subunit protein
receptor of activated C kinase 1 (RACK1). Although we know ribosome specification plays a key role in
selectively regulating poxviral protein synthesis, it is unclear how negative charge in the loop regulates mRNA
selectivity of poxvirus-customized ribosomes and how this selectivity is influenced by global changes in cellular
transcriptional and translational activity during infection. Using structure modeling and biochemical approaches,
we have previously shown that charge in the RACK1 loop increases repulsive electrostatic interactions with the
negatively charged backbone of 18S rRNA near the mRNA exit channel. Therefore, we hypothesize that
introduction of negative charge remodels the loop or mRNA exit channel to more broadly regulate translation by
altering recognition of specific 5’ UTR elements, such as polyA leaders. We will address this hypothesis by
developing two complementary cell systems that we will use to study RACK1-loop mediated mRNA selectivity
under different conditions that mimic aspects of poxvirus infection. We will use polysome profiling and RNA-Seq
to analyze global changes in translational efficiency to gain a broader understanding of transcript-specific
translation modulated by the RACK1 loop. The findings from the proposed research will lay a solid foundation
for our understanding of how poxviruses control translation, as well as future studies of ribosome-centric modes
of translation regulation in diverse biological and pathological contexts.

## Key facts

- **NIH application ID:** 10066664
- **Project number:** 1F31AI152548-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Madeline Grace Rollins
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-06-25 → 2022-06-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066664

## Citation

> US National Institutes of Health, RePORTER application 10066664, RACK1-mediated control of mRNA selectivity by poxviruses (1F31AI152548-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066664. Licensed CC0.

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