# Kinase Regulation of Nuclear Speckle Function and Splicing during Influenza Virus Infection

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $561,137

## Abstract

PROJECT SUMMARY
The goals of this proposal are to uncover how pre-mRNA splicing and nuclear speckles are controlled by
the kinase TAO2, and to determine why TAO2 is required for successful Influenza virus (IAV) replication.
Recent work has identified the understudied protein kinase TAO2 as a host factor essential for splicing and
speckle localization of the IAV M RNA. A pool of TAO2 localizes to nuclear speckles and its loss, by
chemical inhibition or protein depletion, alters nuclear speckle composition, splicing and export of IAV M
RNA, and therefore impairs IAV replication. Inhibition of TAO2 also disrupts splicing of a subset of host
mRNAs, without altering bulk host mRNA. These data uncover a new cellular activity for TAO2 and identify
inhibition of TAO2 as a potential approach for controlling IAV infection. Preliminary data suggest that TAO2
interacts with several splicing factors and other RNA binding proteins. The work outlined in this proposal
seeks a comprehensive understanding of the nuclear activities of TAO2 in human cells and the functional
consequence of these activities for host and viral RNA expression. Specifically, a three-pronged approach
will be taken to: (1) characterize functional TAO2 interaction partners and substrates of phosphorylation
amongst nuclear proteins and determine if IAV infection alters these interactions or if TAO2 interacts
directly with any IAV-encoded proteins; (2) define the role of TAO2 in maintaining the integrity of nuclear
speckles and (3) characterize the global impact of TAO2 on the human splicing machinery and the
consequence of this function for alternative splicing. These goals will be achieved through a combination
of genetic manipulation of cells, biochemistry, mass spectrometry and microscopy. Importantly, the
conclusions obtained from these studies will have implications for general mechanisms of RNA splicing
and nuclear speckle formation and function and will further inform the understanding of host requirements
and vulnerabilities for influenza infection.

## Key facts

- **NIH application ID:** 10911326
- **Project number:** 5R01AI125524-09
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MELANIE H. COBB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $561,137
- **Award type:** 5
- **Project period:** 2016-05-25 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911326

## Citation

> US National Institutes of Health, RePORTER application 10911326, Kinase Regulation of Nuclear Speckle Function and Splicing during Influenza Virus Infection (5R01AI125524-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10911326. Licensed CC0.

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