Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating the role of DDX3 in regulating RNA structure and mRNA export

Award Number: F30HD110250
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Investigating the role of DDX3 in regulating RNA structure and mRNA export - PROJECT SUMMARY/ABSTRACT Mutations in DDX3X are associated with autism spectrum disorder, brain malformations, and epilepsy, and account for up to 3% of cases of females with unexplained intellectual disability. However, little is currently known about the molecular mechanism linking DDX3X mutations to neurodevelopmental disease. DDX3X encodes an RNA helicase of the DEAD-box protein family and has been implicated in many aspects of RNA metabolism, yet we still lack a mechanistic understanding of DDX3X’s role in these processes, as well as how patient mutations in DDX3X affect RNA metabolism. To address this gap in knowledge of understanding of how DDX3X mutations perturb cellular function and contribute to neurodevelopmental disease, we will investigate the mechanism of how DDX3X regulates its target transcripts both at the level of translation initiation and mRNA nuclear export, and study how pathogenic mutations in DDX3X alter these processes. DDX3X is implicated in translation initiation as it binds to 5’UTRs of mRNAs, and is required for the efficient translation of a subset of mRNAs with structured 5’UTRs. However, we still do not know the mechanism of how DDX3X can regulate the translation of these mRNAs. In addition to its role in translation, DDX3X has been implicated in nuclear mRNA processing, and our preliminary data show that the genes in the mRNA export pathway are genetic interaction partners of DDX3X. However, we still do not understand what the function of DDX3X is in the nucleus or mRNA export. We hypothesize that DDX3X regulates its target transcripts through both unwinding secondary structures in their 5’UTRs and chaperoning their nuclear export. To answer this hypothesis, in our first aim we will determine how DDX3X impacts mRNA transcript structure and ribosome engagement by measuring RNA secondary structure through in vivo structure-specific chemical modification and high-throughput sequencing. In our second aim, we will determine the function of DDX3X in the nucleus by examining nuclear export of DDX3X -sensitive mRNAs using RNA FISH staining. Upon successful completion of the proposed experiments, we will have gained a greater understanding the precise mechanism of how DDX3X regulates RNA metabolism both at the level of translation initiation as well as mRNA export. This knowledge is critical for advancing our knowledge of RNA metabolism, as well as understanding and developing treatments for patients with DDX3X syndrome.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	001	4	8/20/2025	NON-COMPETING CONTINUATION	$54,538
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	000	3	11/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	000	3	8/23/2024	NON-COMPETING CONTINUATION	$53,974
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $39,861 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	000	2	7/21/2023	NON-COMPETING CONTINUATION	$39,861
														Subtotal = $39,861

Issue Date FY: 2022 ( Subtotal = $38,682 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	001	1	8/8/2022	NEW	$0
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	000	1	8/8/2022	NEW	$38,682
														Subtotal = $38,682

Grand Total All Awards = $187,055

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the role of DDX3 in regulating RNA structure and mRNA export

Award Number: F30HD110250

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer