# DNA transposons and alternative pre-mRNA splicing.

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $723,205

## Abstract

NIH R35 GM118121; DNA transposons and alternative pre-mRNA splicing. D. Rio – PI.
PROJECT SUMMARY / ABSTRACT
DNA transposons and alternative pre-mRNA splicing. D. Rio – PI
 Mobile genetic elements or transposons are found in the genomes of all organisms. These
elements can move via DNA or RNA intermediates. About 50% of the human genome is made up of
transposable elements with ~ 2.7% corresponding to DNA-based transposons. Many of these
putative transposons or transposase-related genes are uncharacterized. Our previous studies have
focused on the P element family of DNA transposons in Drosophila. P element transposase functions
as a tetramer, using GTP as a cofactor for transposition. N-terminal domain of the transposase
corresponds to a C2CH THAP DNA binding domain, which is a member of a prevalent family of DNA
binding domains found exclusively in animal genomes. One THAP gene, called THAP9, is
homologous to the Drosophila P element transposase and is present in primates, Xenopus, zebrafish
and Ciona, but is absent from rodents. Recent work from our lab has shown that the human and
zebrafish THAP9 genes can mobilize the Drosophila and zebrafish P element transposons in human
and Drosophila cells. We have also used cryo-EM to solve the structure of the P element
transposase strand transfer complex. This proposal is focused on understanding what role the human
THAP9 gene may play in human embryonic stem cells and the reaction pathway that the Drosophila
P element transposase protein uses to recognize and assemble with the transposon ends, donor
DNA, target DNA and GTP/Mg2+ to form an active protein-DNA complex. These studies are aimed at
gaining mechanistic insights.
Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in
metazoans and is a conduit through which genomic sequence is transferred to proteomic information.
Most eukaryotic genes are split and have the potential for alternative splicing, dramatically increasing
proteomic diversity. Many human and mouse disease gene mutations affect the splicing process. in
fact, somatic mutations in splicing factor and spliceosomal genes have been linked to human
diseases, such as cancer and the neurodegenerative disease amyotrophic lateral sclerosis (ALS).
Our previous work has focused on characterization of the tissue-specific Drosophila P element pre-
mRNA exonic splicing silencer element. Recent work from our group has focused on how the action
of the RNA binding proteins, PSI and hrp48 and the human RNA binding splicing factors hnRNPA1
and DDX5. We are using this information to identify new Drosophila cellular splicing silencer elements
that are controlled by PSI and hrp48. We are also analyzing mutant forms of hnRNPA1 that are
linked to ALS to find splicing pattern defects that could be used as biomarkers for the disease or
provide clues to have neurons are dying in the disease. Splicing silencers are a major type of RNA
control element generating tissue- or cell...

## Key facts

- **NIH application ID:** 10086757
- **Project number:** 2R35GM118121-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** DONALD C RIO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $723,205
- **Award type:** 2
- **Project period:** 2016-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086757

## Citation

> US National Institutes of Health, RePORTER application 10086757, DNA transposons and alternative pre-mRNA splicing. (2R35GM118121-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10086757. Licensed CC0.

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