# Mechanisms of Post-transcriptional Gene Regulation by RNA Binding Proteins

> **NIH GM R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2026 · $801,043

## Abstract

PROJECT SUMMARY/ABSTRACT
This MIRA award supports our studies of how RNA binding proteins regulate alternative splicing and other
posttranscriptional steps in mammalian gene expression. The previous funding period was very productive with
multiple publications. We developed new methods and we discovered new interactions and new functions for
several proteins and RNAs. We propose to continue these studies applying our strategy for isolating splicing
regulatory complexes and snRNPs from the chromatin compartment of cells, characterizing their components,
determining their structures, and testing their impact on splicing regulation or other processes. We will complete
our structure by cryo-electron microscopy of chromatin-isolated U2 snRNP’s associated with the epitope-tagged
RBM5 regulator and bound to intron branchpoints. We will go on to determine the structures of U2 particles
associated with tagged SF3A2 and other factors. These structures will provide new insight into how regulators
like RBM5/10 and the RNA Helicase DHX15 alter splicing at a late stage of spliceosome assembly. We will apply
our method of chromatin extraction to new molecules including the U1 snRNP and polypyrimidine tract binding
protein 1. We expect to identify new interactions of these molecules by isolating them bound to their nascent
RNA substrate. These particles also will be examined by EM to assess their suitability for structure determination.
We will continue our studies of the Rbfox family of splicing regulators. Earlier studies of chromatin associated
Rbfox1 demonstrated its association with a complex of other RNA binding proteins (LASR) and its higher order
assembly through homomeric interactions of its disordered C-terminal domain. We will continue our analysis of
the residues that mediate this homomeric interaction and define a minimal segment conferring self-assembly.
Results from this analysis will enable manipulations of Rbfox/LASR assembly in vivo and studies of the role of
thes

## Key facts

- **NIH application ID:** 11335746
- **Project number:** 5R35GM136426-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Douglas L Black
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $801,043
- **Award type:** 5
- **Project period:** 2020-04-01T00:00:00 → 2030-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11335746

## Citation

> US National Institutes of Health, RePORTER application 11335746, Mechanisms of Post-transcriptional Gene Regulation by RNA Binding Proteins (5R35GM136426-07). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/11335746. Licensed CC0.

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