# Interactions Between Pum1 and microRNAs in Cerebellar Ataxia

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $411,990

## Abstract

The heterogeneous nature of the genetic causes of ataxias and related disorders
severely impedes the advancement of specific cures. Since genetically classified ataxia
subtypes are often indistinguishable by clinical diagnosis, common pathological
pathways are likely at play, and understanding the shared underlying mechanisms is a
crucial direction of research. We have identified a novel mechanism of combinatorial
post-transcriptional regulation between two disparate genes implicated in ataxia, PUM1
and VLDLR, and propose to investigate its role in a mouse model. Both PUM1 and
VLDLR mutations have been independently found to cause cerebellar ataxia.
Preliminary data shows that PUM can regulate the VLDLR 3' UTR through co-regulation
with miRNAs. Therefore, elucidating the mechanistic connections between these ataxia-
related genes promises to provide a more coherent view of disease development, to
pinpoint key targets for therapeutic intervention, and to suggest methods of their control.
The conceptual innovation of the proposed work resides in investigating a novel
paradigm of combinatorial post-transcriptional control between RBPs and miRNAs, and
its dysregulation, in mediating cerebellar ataxia. Furthermore, the study is significant
because it aims to uncover new mechanistic insight into the connections between very
recently identified factors in the disease. Achieving the specific aims of this proposal will
provide a solid foundation for further major proposals studying the mechanism of PUM1
/ miRNA interaction on the VLDLR mRNA and the means of its modulation.

## Key facts

- **NIH application ID:** 10042417
- **Project number:** 1R21NS118390-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** FEDOR V KARGINOV
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $411,990
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042417

## Citation

> US National Institutes of Health, RePORTER application 10042417, Interactions Between Pum1 and microRNAs in Cerebellar Ataxia (1R21NS118390-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10042417. Licensed CC0.

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