# Disruption of Cellular RNA Processing by Kaposi's Sarcoma-Associated Herpesvirus

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $366,761

## Abstract

ABSTRACT
 Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of the majority of AIDS-
associated cancers. It is endemic in many areas of Africa where, due to the extraordinarily high HIV
burden, Kaposi sarcoma has emerged as one of the most common cancers on the continent. During AIDS-
induced immunosuppression, KSHV replication is no longer effectively controlled, and, together with a
large latently infected population of cells, contributes to disease progression. During lytic replication,
KSHV and the closely related model murine gammaherpesvirus MHV68 dramatically remodel the host
gene expression environment. Key to this remodeling is its virally encoded, messenger RNA (mRNA)
specific endonuclease termed SOX, which accelerates degradation of a broad spectrum of mRNAs. SOX
activity plays diverse roles in the in vivo gammaherpesvirus lifecycle and immune evasion. However, the
mechanisms underlying the RNA target specificity of SOX remain largely unknown, despite their
prominent roles in shaping the mRNA abundance profile during infection. Our data show that SOX uses a
combination of RNA sequence and structure to capture a broad set of mRNA targets while preserving
selectivity. In Aim 1, we will probe how novel protein-protein interactions between SOX and components
of the RNA processing machinery influence the susceptibility of mRNAs to endonuclease targeting across
a range of cell types. We will then define the downstream consequences of mRNA targeting by SOX,
including how large scale changes to mRNA degradation cause profound ‘ripple effects’ to the gene
expression landscape. In Aim 2, we will mechanistically characterize a new pathway we discovered in
mammalian cells that functionally links the last stage of the mRNA lifecycle (degradation) to the first
stage (transcription). This mRNA decay-transcription “feedback” pathway is activated by SOX and results
in a large-scale reduction of RNA polymerase II occupancy selectively across the mammalian but not the
viral genome. Findings derived from this proposal should have a sustained impact on the field of
gammaherpesvirus biology, and change current perceptions on how stress or virus-induced alterations to
mRNA stability influence seemingly distal components of the gene regulation circuitry.

## Key facts

- **NIH application ID:** 10840477
- **Project number:** 5R01CA136367-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Britt A Glaunsinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,761
- **Award type:** 5
- **Project period:** 2010-05-12 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840477

## Citation

> US National Institutes of Health, RePORTER application 10840477, Disruption of Cellular RNA Processing by Kaposi's Sarcoma-Associated Herpesvirus (5R01CA136367-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10840477. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*