PXD056482

PXD056482 is an original dataset announced via ProteomeXchange.

Title	SINEUP RNA rescues molecular phenotypes associated with CHD8 suppression in Autism Spectrum Disorder model systems
Description	Loss-of-function mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are strongly associated with Autism Spectrum Disorders (ASD). Indeed, the reduction of CHD8 causes transcriptional, epigenetic and cellular phenotypic changes, correlated to disease that can be monitored in assessing new therapeutic approaches. SINEUPs are a functional class of natural and synthetic antisense long non-coding RNAs able to stimulate the translation of antisense target mRNA, with no effect on transcription. Here we employed synthetic SINEUP-CHD8 targeting the first and third AUG of the CHD8 coding sequence to efficiently stimulate endogenous CHD8 protein production. SINEUP-CHD8 were effective in cells with reduced levels of the target protein and in patients’-derived fibroblasts with CHD8 mutations. Functionally, SINEUP-CHD8 were able to revert molecular phenotypes associated with CHD8-suppression, i.e. genome-wide transcriptional dysregulation, and the reduction of H3K36me3 levels. Strikingly, in chd8-morpholino-treated and ENU mutant zebrafish embryos, SINEUP-chd8 injection confirmed the ability of SINEUP RNA to rescue the chd8-suppression-induced macrocephaly phenotype and neuronal hyperproliferation. Thus, SINEUP-CHD8 molecule(s) represent a proof-of-concept towards the development of a novel RNA-based therapy for neurodevelopmental syndromes with implications for, and beyond ASD, and relevant to genetic disorders caused by protein haploinsufficiency.
HostingRepository	PRIDE
AnnounceDate	2025-02-24
AnnouncementXML	Submission_2025-02-24_00:19:10.790.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056482
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Romina Belli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-03 07:46:45	ID requested
⏵ 1	2025-02-24 00:19:11	announced

10.6019/PXD056482;

submitter keyword: CHD8

SINEUP

autism spectrum disorders (ASD)

lncRNA

neurodeveloment

Zebrafish

Marta Biagioli
contact affiliation	NeuroEpigenetics laboratory, Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
contact email	marta.biagioli@unitn.it
lab head
Romina Belli
contact affiliation	University of Trento
contact email	romina.belli@unitn.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056482
     1. Label: PRIDE project
     2. Name: SINEUP RNA rescues molecular phenotypes associated with CHD8 suppression in Autism Spectrum Disorder model systems