PXD054548-1

PXD054548 is an original dataset announced via ProteomeXchange.

Title	Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown
Description	Neurons rely on mRNA transport and local translation to facilitate rapid protein synthesis in processes far from the cell body. These processes allow precise spatial and temporal control of translation and are mediated by RNA binding proteins (RBPs), including those known to be associated with neurodegenerative diseases. Here, we use proteomics, transcriptomics, and microscopy to investigate the impact of RBP depletion on mRNA transport and local translation in iPSC-derived neurons. We find thousands of transcripts enriched in neurites and that many of these transcripts are locally translated, possibly due to the shorter length of transcripts in neurites. Loss of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS)-associated RBPs TDP-43 and hnRNPA1 lead to distinct alterations in the neuritic proteome and transcriptome. TDP-43 knockdown (KD) leads to alternative splicing in neurites and increased neuritic translation. In contrast, hnRNPA1 leads to more moderate effects on local mRNA profiles and alternative splicing, possibly due to compensation by hnRNPA3. These results highlight the crucial role of FTD/ALS-associated RBPs in mRNA transport and local translation in neurons and the importance of these processes in neuron health and disease.
HostingRepository	PRIDE
AnnounceDate	2025-07-30
AnnouncementXML	Submission_2025-07-30_11:45:20.208.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ziyi Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-02 15:44:27	ID requested
⏵ 1	2025-07-30 11:45:21	announced

Dargan R, Mikheenko A, Johnson NL, Packer B, Li Z, Craig EJ, Sarbanes SL, Bereda C, Mehta PR, Keuss M, Nalls MA, Qi YA, Weller CA, Fratta P, Ryan VH, Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown. bioRxiv, ():(2024) [pubmed]

10.1101/2024.09.26.615153;

submitter keyword: Human,iPSC derived iNeurons

Andy Qi
contact affiliation	Center for Alzheimer’s Disease and Related Dementias (CARD) National Institutes of Health (NIH)
contact email	andy.qi@nih.gov
lab head
Ziyi Li
contact affiliation	NIH
contact email	liz36@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054548
     1. Label: PRIDE project
     2. Name: Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown